Annual Report 2016-2017 - RCPCH · Annual Report 2016-2017. ... - Female genital mutilation 14 -...

Royal College of Paediatrics and Child Health5-11 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).

BPSU British Paediatric Surveillance Unit

Annual Report 2016-2017

Aims of the British Paediatric Surveillance Unit

To:

• Facilitate research into uncommon childhood infections and disorders for the advancement of knowledge and to effect practical improvement in prevention, treatment and service planning

• 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

• 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

1BPSU Annual Report 2016-2017

Contents

Foreword 2

By Dr Richard Reading 2 Chair, BPSU

1. How the Surveillance 3 System Works

- Background 3

- Selection of studies for inclusion in the scheme 3

- The reporting system 3

- Follow-upandconfirmationofcase reports 3

2. Scientific Coordinator’s 4 Yearly Review of Activities

- Participation in the scheme during the 4 year 2016

- Public and patient engagement 4

- International activities 4

- Funding 4

- Regional response study outcomes 5

3. Surveillance Studies 6 Undertaken in 2016

- AttentionDeficitHyperactivityDisorder 6 in transition from children’s services to

adult services

- Behçet’s syndrome 8

- Congenital rubella 10

- Congenital Zika syndrome 12

- Female genital mutilation 14

- HIVinfection&perinatal 16 HIVexposure

- Nutritional rickets 20

- Pierre Robin sequence 22

- Progressiveintellectual& 25 neurological deterioration in children (Including Creutzfeldt - Jakob disease)

- Visualimpairmentandblindness 27

Appendix 29

- Publications2016-17 29

- Presentations2016-17 30

2 BPSU Annual Report 2016-2017

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 inBirminghamwhichwasfilled,almostliterally,totheraftersofthelecturetheatre.We continue to host the Rare Disease Day tea party and Richard Lynn, our scientificcoordinator, is increasingly involvedwith the rarediseasemovement.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.

Somespecificimpactsofthisyear’sworkincludecontributionstotheNationalScreeningCommittee’sdeliberations on Group B strep screening, and the rapid implementation of surveillance for congenital Zikasyndrome.TheBPSUwasthefirstsurveillanceunitinthedevelopedworldtosetupsurveillanceand 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 willsettheZikasurveysintoacontextofothercausesofmicrocephaly.

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 separatesystems 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, pleaserememberthatitwouldbeawholelotworsewithoutthehelpoftheBPSUoffice,andwearestillworking on making this ever easier. One way of doing this is to work towards collecting and storing data electronicallyinasecure“safehaven”.Wehopetomakesignificantprogressonthisinthenextyear.

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 yourcontinued support.

Dr Richard Reading Chair, BPSU

Foreword

Richard Reading. Chair BPSU, November2017

BPSU Annual Report 2016-2017 3

BackgroundRare 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 foraffected children, their families and health systems.

To address this problem in the UK and Ireland, the BPSU was set up in July 1986, enablingpaediatricians 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: theRoyalCollegeofPaediatricsandChildHealth(RCPCH), Public Health England, UniversityCollegeLondon-InstituteofChildHealth,GOSHChildren’s Charity and the Faculty of Paediatrics of the Royal College of Physicians of Ireland. The BPSU’s Scientific Committee meets six times ayears to consider individual applications and the progress of studies.

Selection of studies for inclusion in the schemeDetails on the selection process and application process for the BPSU is now available online at http://www.rcpch.ac.uk/bpsu/apply.

EachapplicationrequiresapprovalfromtheBPSUScientificcommittee,aResearchEthicsCommittee(REC), theConfidentialityAdvisoryGroup (CAG)oftheHealthResearchAuthorityandtheScottishPublicBenefitsandPrivacyPanel(PBPP).

The reporting systemSurveillance is ‘active’ in that the BPSU officeactively sends out an electronic orange card (eCards) to consultant paediatricians in the UK and Ireland asking for cases to be reported on the BPSUorange‘eCard’(Figure1).Eachmonth,allclinicians 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 completingthecard,includingthecasedefinitionofthe 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.

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

Follow-up and confirmation of case reports

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 fullyanonymised,theamountofpatientidentifiabledata collected is strictly limited to preserve patient confidentiality.Thestudyinvestigatorsreportbackto the BPSU indicating when cases have been confirmedorareduplicatecasereports(seeFigure2). 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.

Toimprovecaseascertainmentforspecificstudieswhere 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.

How the Surveillance System Works1Figure 1: Orange Card

Figure 2: Surveillance mechanism


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 toepilepsy, Dr Omar Abdel-Mannan, UCL GOS Institute 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, progressiveintellectual and neurological deterioration, female genital mutilation and Behçet’s syndrome.

During2016-17,therewere16publicationsrelatingto BPSU studies and 22 conference presentations (see Appendices, p.31).

Participation in the scheme during the year 2016Reporting rates for returning the orange‘eCards’ remain high - the overall card return compliance rate for the year 2016, calculated as aproportionoforangecardsreturned,was94.2%(39,545/41,987)afallof0.1%from2016.Monthlyresponserates ranged from95.2% inJanuary to93.2%inNovemberwithamediaof94.4%.Detailsof 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 follow-up 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 willhave 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: 798of3,577 (22%) receivinga card reporteda case in2016.14%(514)reportedasinglecase,6%(218reportedbetweentwoandfourcasesand2%(66)reportedfiveormorecases.Thegreatestnumberofcases reportedwasbyHIVspecialists,oneofwhom reported 68 cases.

Public and patient engagement

The BPSU is committed to wider public patient engagement (PPE) in the development anddissemination 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, theBPSU in collaborationwithRare 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 launcheditsRareTogether initiative.Theaim is to act as a conduit for children and young people affected by rare disease to communicate. Our first activity is toworkwithRareRevolution

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 paediatricsurveillance 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 heldinparallelwiththeRCPCHscientificmeetinginGlasgow on 12-13th March 2018. More information at http://www.inopsu.com/conference2018.

FundingBPSU is currently funded through grants from UCLGOSInstituteofChildHealth,RCPCH,andPublicHealthEnglandwithadditionalsupportfromGreat Ormond Street Children’s Charity and with contributions from researchers.

Richard Lynn,ScientificCoordinator

Scientific Coodinator’s Yearly Review of Activities2

2017inpictures-higlightsfromtheBPSU


Region % return Rank 2016 Rank 2015

EastAnglia 96.4% 1 2

Mersey 93.6% 13 12

NET 92.0% 20 19

North Scotland 95.7% 5 1

North Western 95.2% 7 18

Northern 93.5% 15 5

Northern Ireland

92.9% 16 17

NWT 92.6% 19 13

Oxford 94.0% 12 11

Republic of Ireland

92.6% 18 20

SET 92.9% 17 15

South Scotland 95.9% 3 8

South Western 95.0% 9 14

SWT 96.0% 2 4

Trent 93.5% 14 9

Wales 94.2% 11 7

Wessex 95.1% 8 10

West Midlands 94.9% 10 10

West Scotland 95.6% 6 3

Yorkshire 95.8% 4 6

Table 1: Regional Response rate 2015 and 2016

Condition under

surveillance

Date when reporting

began

Validreports % Duplicates Errors (D&E)% Not yet

known % Total

HIV Jun-86 8,982 75 880 763 14 1,377 11 12,002

CRU Jun-91 93 46 42 63 52 3 2 201

PIND May-97 2,253 55 532 1,094 39 258 6 4,137

RKT Mar-15 124 45 5 88 34 57 21 274

BEH May-15 62 52 15 33 41 8 7 118

ARF May-15 17 28 5 6 18 32 53 60

VIB Oct-15 173 51 8 80 26 76 23 337

FGM Nov-15 41 62 3 16 29 6 9 66

ADHD Nov-15 219 61 0 81 23 56 16 356

PRS Jan-16 112 62 27 8 19 34 19 181

EPI Nov-16 36 69 0 0 0 16 31 52

CDD Nov-16 0 0 0 0 0 4 100 4

Total 12,112 68 1,517 2,232 21 1,927 11 17,788

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

Figure 3: Regional Response rate 2016

HIV HIVinfectionandperinatalHIVexposureCRU Congenital rubella PIND Progressive intellectual and neurological deteriorationEBT NeonatalexchangebloodtransfusionRKT Nutritional ricketsBEH Behçet’s syndrome

ARF Acute rheumatic feverVIB VisualimpairmentandblindnessFGM Female genital mutilationADHD AttentiondeficitandhyperactivitydisorderPRS Pierre Robin SequenceEPI Deathsinchildrenwithepilepsy(excl.Scotland)CDD Childhood disintegrative disorder


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.

Surveillance Studies Undertaken in 20163

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

SummaryThis project focuses on what happens to young peoplewithAttentionDeficitHyperactivityDisorder(ADHD) when they are too old to stay withchildren’s services. Little is known about how many areas have specialist services for adults withADHDandhowmanyyoungpeopleneedtomove to them when they are too old for children’s services. Until the late twentieth century ADHDwas 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 ADHDandcontinuetowantsupporttocopewiththeir lives.

There are National Institute for Health andCare Excellence (NICE) guidelines about themanagement for ADHD in adulthood, and thisoften involves taking medication that General Practitioners feel inexperienced to prescribewithout support from specialists, as happens with children. Existingwork suggests that youngpeople with developmental disorders like ADHDare 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 howmany young people are in need of services for ADHDasadults.A13monthssurveillancestudytriedtofindoutwhathappenstoyoungpeoplewithADHD onmedicationwho arewithin sixmonthsof the age-boundary for discharge from their children’s service.

Surveillance periodNovember 2015 - November 2016 (inclusive). Follow-up period: Follow-up questionnaire at nine monthsafterinitialdiagnosis,endinginAugust2017.

MethodologyData capture used a dual surveillance methodology using the Child and Adolescent Psychiatry Surveillance System (CAPSS) in additiontotheBPSU,to identifycasesofADHD;details of the study protocol are available at http://www.rcpch.ac.uk/bpsu/adhd

Analysis

As of June 2017 there have been 350 BPSUnotifications, 259 returned questionnaires, 218ofwhich are eligible.CAPSShave reported 349notificationsofwhich161havebeenreturned,132of which are eligible.

There have been 90 cases (42 BPSU and 48CAPSS) that have been reported in error and are not eligible and therefore the questionnaire will not be returned. Currently the response rates are 86%forBPSUand60%forCAPSSwhichisveryencouraging.

DiscussionThis is a novel approach to the surveillance study asranbyBPSUandCAPSS;thisstudyexploresthe incidence of a transition of a young person withADHDbetweenchildren’sservicesandadultservices.

It is too early to report on the study results and reflectonthemethodusedtoanswerthisresearchquestion. 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

Professor Tamsin Ford


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.


UKADHDNetwork(UKAAN)andAdultAttentionDeficitDisorderUK(AADD-UK)Web: https://www.ukaan.org; https://aadduk.org

FundingThisstudyisfundedbyNationalInstituteforHealthResearch (NIHR) Health Services and DeliveryResearch Programme funding (14/21/52). See: https: / /www.journalsl ibrary.nihr.ac.uk/programmes/hta/142152#/

Researcher contacts

Professor Tamsin Ford, Professor of Child and AdolescentPsychiatry,UniversityofExeterMedicalSchool,SouthCloisters,StLuke’sCampus,ExeterEX12LUTel:01392722973Email:[email protected] Co-investigatorsImperial College London: Dr Cornelius Ani, Dr Susan YoungKing’s College London: Professor Philip AshersonUniversityofExeter: Dr Astrid Janssens, Dr Tamsin Newlove-Delgado, Dr Catherine Shotton, Professor Stuart Logan, HelenEkeUniversity of Nottingham: ProfessorKapilSayal,ProfessorChrisHollisUniversity of Warwick: Dr Moli PaulUniversity of York:Professor Bryony BeresfordCerebra, Charity organisation: TracyElliot


Behçet’s syndromeKey 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.

SummaryBehçet’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 cansometimes 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 carefromdoctorswithexpertiseinthiscondition. We hope that the results of this study will have benefits for future children with the condition byproviding us with more information on how many

children are affected and how Behçet’s syndrome makes them ill. In particular, we currently do not know howmany children have eye inflammationor whether we should routinely screen children for eyeinflammationeveniftheyhavenosymptoms.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 thecondition and what to expect to children andfamilies.

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

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

Dr Clare Pain

Clinical teams involved Paediatric Rheumatologist 44/89.8%

Ophthalmologist 38/77.6%

General Paediatrician 30/61.2%

OralMedicine/PaediatricDentist 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%

Medication Systemic treatment 35/71.4%

Topical treatments only 7/14.3%

No treatment 6/12.2%

Not known 1/2.0%

Outcomes Controlled on medication 29/59.2%

Active disease despite medication 11/22.4%

Stable off medication 5/10.2%

Not known 4/8.2%

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


Analysis

TotheendofApril2017(24months),138caseswerenotifiedand83completedquestionnairesanalysed(49 cases excluded: 35 errors; 14 duplications;22questionnairesyettobecompleted).49oftheanalysedcasesareconfirmedBehçet’ssyndrome,defined as an International Criteria for Behçet’sDisease (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 definiteBehçet’s;probable/incompleteBehçet’s;ornot Behçet’s. Cases which are reviewed as being probable/incompleteanddefiniteBehçet’swillbeincludedinthefinalresearchfindings.

Twenty-seven(55%)ofthecaseswerefemaleand22(45%)male.Meanageatpresentationwas9.1years and diagnosis 10.1 years.

With regards ethnicity, 40 (81.6%) cases werewhite,four(8%)werefromPakistaniorigin,higherthan the population, with one (2%) from Indian,Black,mixedandother.

Children presented with a wide array of clinical manifestations – 49 (100%) with oral ulceration,45(91.8%)withgenitalulceration22(44.9%)withskin involvement, 11 (22.4%) eye involvementwhilst neurological and vascular involvement waslesscommonaffectingsix(12.2%)andthree(6.1%) respectively. The most common othermanifestations were arthralgia and arthritis, both five(10%)andabdominalpainfour(8%).

Thirty-nine (79.6%)of the49childrenwereseenby three or more different specialities depending ondiseasemanifestations.Onlysix(12.2%)werenot on regular treatment, seven (14.3%) weremanaged on topical treatment only, 35 (71.4%)required systemic immunosuppression and 11 (22.4%) had active disease despite medication(Table 3).

Discussion

The 49 children confirmed as having Behçet’shave a wide array of clinical manifestations. Recurrent oral ulceration is the most common, thengenitalulcerationandskininvolvement.Eye,neurological and vascular involvement are all less common. On average there is one year between firstpresentationanddateofdiagnosis.

There is a family history of Behçet’s syndrome in a first degree relative in 13 (26.5%) and

in a non-first degree relative in five (10.2%). This study highlights the extreme rareness ofBehçet’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 examplealowfrequencyofeyeinvolvement.Thehigh number of specialists involved in the case of the children shows that they have complex careneeds.


Behcet’s Syndrome SocietyWeb: http://www.behcets.org.uk/

FundingThis study is funded by Alder Hey Children’sCharity, Behcet’s Syndrome Society Charity (from funds raised by the Worshipful Company ofHorner’s),ProfessorFaridaFortune,ProfessorRobertMootsandVasculitisUK.

References1. Dejaco, C. et al, Meeting report of 13th international conference on Behçet’s Disease. The JournalofRheumatology,2009.36(6)1312-1317;DOI:https://doi.org/10.3899/jrheum081008

2. Zouboulis,CC.etal,EpidemiologicalFeaturesof Adamantiades-Behçet’s Disease in Germany and in Europe. Yonsei Medical Journal, 1997.38(6):411-422

3. International Team for the Revision of the International Criteria for Behçet’s Disease (ITR-ICBD), The International Criteria for Behçet’s Disease (ICBD). J EurAcadDermatol Venereol.2014.28:338-347

Researcher contacts Dr Clare Pain, Consultant Paediatric Rheumatologist, Alder Hey Children’s NHSFoundationTrust,EatonRoad,Liverpool,L122APTel: 0151 282 4521E-mail: [email protected]

Co-investigators

UniversityHospitalAintree: Professor Robert MootsGreatOrmondStreetHospital:DrPaulBroganQueen Mary’s School of Medicine and Dentistry:Professor Farida FortuneQueen’s Medical Centre, Nottingham:Dr Ruth MurphyUniversity of Liverpool: Professor Michael W. Beresford


Congenital rubellaKey points• Since 2005, 12 congenital rubella births have been reported in the UK; none were reportedbetweenApril2015andMarch2017.• 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 wasdiscontinuedinEnglandinApril2016.

SummarySurveillance of congenital rubella (CR) has been inplacesince1971,whentheNationalCongenitalRubella Surveillance Programme (NCRSP) was set up to monitor the impact of rubella vaccine; there has been active surveillance throughout the UKandIrelandthroughtheBPSUsince1990.Thelast 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 inApril 2016 (andsubsequently also in Scotland and Wales) but continues in Northern Ireland and in the Republic of Ireland.ThePHE’sNationalScreeningProgrammesupports 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 canshed rubella virus foranextendedperiodoftime, and every infected infant must be diagnosed and managed appropriately to avoid the risk of contributing to further community transmission.

AreviewbytheWorldHealthOrganization(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 theWHOAfrican and South-EastAsian regions where vaccine coverage is lowest. InApril 2015 theWHO Region of theAmericasbecame thefirst in theworld tobedeclared freeofendemictransmissionofrubella,andtheWHOaims to eliminate measles, rubella and congenital rubella (elimination defined as <1 case of CRSper 100,000 births) from five of the sevenWHOregions by 2020. Although in the UK reported cases of CRS have been below this level for many years, rubella outbreaks and associated CR births havebeenreportedinseveralEuropeancountriesin the last decade, including Romania, Poland and Italy, and continued vigilance is necessary.

Surveillance period

January1990andisreviewedyearly.

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

AnalysisBetweenApril 2016 andMarch 2017 thereweresix reports to the BPSU. Two of these wereduplicates 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 newlydiagnosed children who were born abroad, in order not to miss any cases, and to contribute to Europeansurveillancedata;noreportsreceivedinthis period related to children born abroad.

Congenital rubella births in the UK or Ireland 1990-2017: 67 children and four stillborn infants withconfirmedorcompatibleCRhavebeenbornandreported since active surveillance was established in 1990; 54 of these (76%) were first reportedthrough the BPSU (Table 4).

Since2005therehavebeen12confirmedreports,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 MMRvaccinationasateenager.Halfofthewomenacquired their infection abroad in early pregnancy, but six came intocontactwith rubella in theUK.

Table 4: Confirmed and compatible congenital rubella births in the UK and Ireland 1990 to March 2017

Primary Source of notificationYear of birth BPSU Other Total1990-94 * ^ 22 10 321995-99 12 4 162000-04 * 10 1 112005-09 * 4 2 62010-17 6 0 6Total 54 17 71* includes a stillborn infant^ includes a set of triplets, one of whom was stillborn

DrHelenBedford


Discussion

Very fewcasesofCRhavebeenreported in thelast decade and most reports concern infants with neonatal symptoms who also have serious rubella-associated defects identified at birth orsoon 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.

FundingThis study is funded UCL GOS Institute of Child Health and the NHS Infectious Diseases inPregnancy Screening (IDPS) programme (PHE).


Sense. Web: http://www.sense.org.uk 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 contactsDr Helen Bedford, National Congenital RubellaSurveillance, Population, Policy & PracticeProgramme, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street London WC1N1EHTel:02079052333E-mail: [email protected]


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

SummarySince May 2015 when Zika virus infections were first confirmed in Brazil, the virus has spread tomany 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

Everyyeara largenumberofUKresidentstravelto 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).

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 the three months before conception.

In the start of the epidemic, very little was known about the disease and, of particular concern, the level of risk infection posed to pregnant women travelling to affected areas and their babies. In light of this uncertainty and the rapid spread of the virus, surveillance of numbers of babies affected by Zika virus infection needed to be established urgently, to estimate the risk to the UK population and, if required, to help planning for services to care for these children.

As one of the BPSU’s main purposes is to facilitate rapid response to public health emergencies and international surveillance of rare diseases, processes were in place to enable timely establishment of surveillance of congenital Zika syndrome in returning travellers in the UK.

At the time of development of this study, the Zika epidemic was a rapidly evolving situation with

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 definitionforsurveillance.

Sincethen, theWHOhasdeclaredanendtothePublicHealthEmergencyofInternationalConcernand, 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.

Methodology

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

Surveillance periodApril 2016 – April 2018 (inclusive). Follow-up period: Follow-up questionnaire at 24 months after initial diagnosis, ending in April 2020.

Analysis

Five suspected cases in total have been reported during the surveillance period. Of those, one case wasexcluded,onediscarded,and threepotentialcases remain under follow up.

Discussion

The number of suspect cases reported was at the lower end of the number of cases we predicted for this time period.

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 madeby 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

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Dr Richard Pebody


by 28thFebruary2017,withnodeclineinaveragenumbers travelling each month. This would indicate that, even though small, there is ongoing potential risk of identifying cases of CZS in the UK despitePublicHealthEngland’srecommendationfor pregnant women to avoid travel to Zika affected countries.

The risk for Zika virus infection has changed sincelastyear.TheWHOdeclaredtheendofthePublicHealthEmergencyofInternationalConcernon 18th November 2016, overall numbers of new cases in affected countries has been declining and no further countries have reported a case of CZS sincebeginningof2017.

However, a large proportion of the Southernhemisphere is now known to be affected by Zika virus transmission, including countries in South East Asia and Africa and the US. To date, 31countries have reported approximately 3,000cases of CZS. This includes travel associated casesintheUS,Canada(2cases)andEurope(1case in Slovenia and 2 cases reported from Spain).

There is also still uncertainty about the level of risk ofhavinganaffectedbabyifawomanwasexposedto Zika during pregnancy. Evidence so far hasbeenconflictingandthereisnoconsensusontherate 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 gapsin knowledge of the natural history of the condition and the on-going transmission of Zika virus, the study was extended until April 2018.

References

1. KrauerF,etal.ZikaVirusInfectionasaCauseof Congenital Brain Abnormalities and Guillain-Barre Syndrome: Systematic Review. PLoS Med 2017;14(1):e1002203

2. Brasil,Petal.ZikaVirusInfectioninPregnantWomen inRiode Janeiro.NEngl JMed2016;375:2321-34

3. Honein,MAetal.BirthDefectsAmongFetusesand Infants of US Women With Evidence ofPossible Zika Virus Infection during Pregnancy.JAMA2017;317(1):59-68

4. Aubry, M et al. Zika Virus Seroprevalence,French Polynesia, 2014-2015. Emerg Infect Dis201723(4):669-672

FundingThisstudyisfundedbyPublicHealthEngland.

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

Researcher contactsDr Richard Pebody, Public Health England, 61ColindaleAvenue,LondonNW95EQTel:02083277423E-mail: [email protected]

Dr Clarissa Oeser, Public Health England, 61ColindaleAvenue,LondonNW95EQTel:02083276729E-mail: [email protected]

Co-investigators

PublicHealthEngland:ProfessorDilysMorgan.DrHilaryKirkbride,DrNickAndrews,DrAndreCharlettHead LeedsGeneralInfirmary: Dr Kathryn JohnsonSt George’s, University of London:ProfessorPaulHeath,DrShamezLadhani,University of Bristol:ProfessorAlanEmond

Figure 5: Zika virus

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Female genital mutilationKey points• The interim data shows that numbers reported to the BPSU are far smaller than expectedfromthepublishedfiguresofestimatedrisk. • Geographical distribution is unexpectedas some large inner cities where there are high numbers from practising communities are not represented. • None of the reported cases were done illegally.

SummaryFemale genital mutilation (FGM) is the name given toproceduresthatinvolvecutting,removingfleshor 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. partialclitoroidectomy, 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 arein 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

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

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

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

Asasecondsourceofascertainment,theSexualAssault 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.

AnalysisDatabasedonanalysisasofApril2017

Of the 55 cases reported to the BPSU in the first year, 29 (53%) had confirmedFGM of which we are awaiting outstanding information, 20 were reported in error, or were duplicates, six questionnaires are incomplete.

DrDeborahHodes

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


Theresultspresentedare interimfindingsonthe29.Of thecompletedquestionnaire items,at thetime of diagnosis all children were older than four years (n=26), most children were diagnosed at 4–6 years(n=7)or13–16years(n=7),followedby7–9years (n=6) and 10–12 years (n=6).

Almost all children were born outside of the UK, in African countries (n=25). For confidentialitypurposes 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).

AhistoryofFGMwasreportedin26(83%)cases,andsuspectedFGMin3(10%)cases.Nochildrenpresented with a history of labioplasty or genital piercing. The circumstances of FGM were known in19casesofwhichseven(32%)wereperformedby a healthcare professional either in a family membershouse/village(n=5)orclinic(n=2).

Discussion

Thefirst yearof reportinghas shown that casesare being found and investigated. The reporting of clinicalpresentationandexaminationfindingscanbe used to educate healthcare professionals and planhealthservices.Thestudyextensionto2017will help to identify the true incidence, presentation and management of cases.

Funding

This study was supported by a grant from the DepartmentofHealth.

References

1. HodesD,PallK,O’DonnellNA,etal.G78(P)Female genital mutilation (FGM) surveillance in under 16 years olds in the UK and Ireland Archives ofDiseaseinChildhood2017;102:A32

Public and patient engagementFORWARD (Foundation for Women’s HealthResearch and Development).Web: http://forwarduk.org.uk

Researcher contacts

Dr Deborah Hodes, University College Hospital,250EustonRoad,LondonNW12BUE-mail: [email protected]

Dr Najette Ayadi O’Donnell, University College Hospital,250EustonRoad,LondonNW12BUE-mail: n.ayadio’[email protected]

Co-investigators

BirminghamChildren’sHospital:DrGeoffDebelleUCLGOSInstituteofChildHealth:ProfessorRussellVinerUniversityCollegeLondonHospitals:Dr Alison Armitage, Professor Sarah CreightonRCPCH:KarinaPall,MarinaLeoniBPSU: Richard Lynn


HIV infection & perinatal HIV exposureKey points• The number of children born each year in the UK and Ireland to women with diagnosed HIVinfectionhasstabilisedinrecentyearsandiscurrently between 1,100 and 1,200; the mother to child transmission rate among diagnosed women isnowbelow0.3%.• 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 auditcircumstances 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 NationalsurveillanceofpaediatricHIVinfectionandperinatalHIVexposureisbasedoncomprehensive,anonymised, paediatric and obstetric reporting. Data from all sources are combined as the National StudyofHIVinPregnancyandChildhood(NSHPC)at the UCL Great Ormond Street Institute of Child Health.1TheNSHPCmonitorschangingpatternsofHIVinfectionanddiagnosisinpregnantwomenand 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 UKand 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 between2007 and 2010. There has been some declinesince then, with around 1,100 births reported each year since 2013.Antenatal HIV screening,introduced as a universal offer from 2000, is takenupbyover95%ofpregnantwomen in theUK,soveryfewHIV-positivewomennowremainundiagnosed at the time of delivery (https://www.gov.uk/government/organisations/public-health-england). By 2009 40% of pregnancieswere a second or subsequent pregnancy since thewoman’sHIVdiagnosis.2 MTCT rates among

diagnosed women have continured to decline from 2.1% in2000-2001 tounder0.5% in2010-20113 andbelow0.3% in2012-14;4 this compares with anestimated20-30%fromundiagnosedwomen.3 Fewer than 10 infants now acquire infection each year in the UK and Ireland, and most of these have motherswhowerenotawareoftheirHIVstatusatthe time of delivery. The circumstances of recent UK-borncaseswereexploredintheNSHPCauditofperinatalHIVinfection.

MethodologyThe BPSU uses its standard methodology and data capture to facilitate the NSHPC paediatricsurveillance. Further details of the BPSU study protocol can be found at http://www.rcpch.ac.uk/bpsu/hivandmoreinformationontheNSHPCathttp://www.ucl.ac.uk/nshpc.

Surveillance periodNational surveillance of paediatric AIDS began in 1986. Surveillancewas extended to includeHIVinfection and perinatal HIV exposure in 1989.Follow-up period: Infection status of perinatally-exposedinfantsisusuallyreportedduringthechild’sfirstyearoflife.Long-termfollow-upinformationonchildrenwithconfirmedHIV infection is collectedthrough the Collaborative HIV Paediatric Study(CHIPS),acollaborationbetweentheNSHPC,theMRC Clinical Trials Unit, and clinicians (https://www.chipscohort.ac.uk).

AnalysisCumulatively there have been 11,593 BPSUreportsby theendof2016.Of these8,905wereconfirmed cases of HIV infection or exposedinfants at risk of vertical transmission; 1,095reports have not yet had status confirmed. Theremaining1,593reportswereduplicatesorerrors.A further 13,205 confirmed cases and exposedinfants have been reported through other sources (see study protocol). The remainder of this report includesverifieddatafromallreportingsources.

By the end of December 2016, 22,166 HIV-infected or exposed children had been reportedtotheNSHPC,20,163(91%)ofthesesince2000(seeTable4).InEngland,theproportionofreportsmade from the London regions has decreased from over70%priorto2000toaroundhalfsincethen. Children born to HIV-positive women: Most

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

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paediatric reports (21,714/22,166, 98%) were ofchildren born to HIV-positive women (Table 5).Ofthesechildren,2,194(10%)wereknowntobeinfected,and17,085(79%)uninfectedbytheendof 2016; infection status for the remaining 2,435 (11%)hadnotyetbeenreported,butthemajoritywere 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.TheNSHPCreportedanoveralltransmission rateof justunder0.3% forbirths todiagnosed women 2012-2014 (7/2,580, 0.27%,95%CI:0.11-0.56%),3 continuing the decline from 0.46%in2010-2011and2.1%in2000-2001.Theprimary 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 non-receipt of antenatal cART. A substantial proportion of pregnancies reported are second or subsequent pregnancies since maternal HIV diagnosis.2 In 2012-201485%ofchildrenwereborntomotherswhowereawareoftheirHIVstatusatconception,over 60% of women conceived on cART, andoverall almost 90% of women delivered withundetectable viral load.4 At the same time there have been changes in the population of pregnant women with HIV in the UK. These include anincreasing number of women aged over 40 years5 and vertically-infected pregnant women. Infected children: Since surveillance started in

1986,2,639childrenwithHIVinfectionhavebeenreported; this includes 267 probably infected inthe course of treatment for haemophilia, all born before 1985 and reported before 1995, leaving2,372 mostly perinatally infected children. Thepopulation 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%ofchildren reportedwithHIV infectionwereborn abroad, the majority in sub-Saharan Africa (89%). Among 2,228 mostly perinatally infectedchildren,266(12%)areknowntohavedied,120(5%)tohavegoneabroadand488(22%)tohavetransferredtoadultservices;afurther275(12%)are lost to follow up. To date there have been over 100 pregnancies in perinatally infected women whowerereportedtotheNSHPCaschildren.

New diagnoses for UK and Irish born children fell from40-50peryear(2000-2006),to20-30(2007-2011), 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 9months (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 declinedfrom6years(IQR:3yr-9yr)forthoseborn

Region of first report 1986-1999 2000-2016 Total

England total London North Midlands & East South

1,5711,118 (71%) 181 (11%) 128 (8%) 144 (9%)

17,3538,446 (59%)2,796 (16%)3,878 (22%)2,233 (13%)

18,9249,5642,9774,0062,377

Wales 26 276 302

Northern Ireland 5 133 138

Scotland 231 627 858

Ireland 170 1,774 1,944

Total 2,003 20,163 22,166

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)

Year of Birth Infected Indeterminate Not infected Total

1984-1999 111 141 898 1,150

2000-2005 62 308 4,629 4,999

2006-2008 27 172 3,888 4,087

2009-2011 16 273 3,813 4,102

2012-2014 8 535 2,878 3,421

2015-2016* 4 926 671 1,601

Total 228 2,355 16,777 19,360

*reports for recent years are subject to reporting delay

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)


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 surroundingperinatal transmissions born and reported since 2006 with the aim of improving antenatal HIVscreening protocols. There were 108 children born since2006confirmed infectedby theApril 2014;of these 41 (38%) were born to diagnosed and67 (62%) to undiagnosed women.7 The number of reports of perinatally infected children born to undiagnosed women during this period is likely to increaseas laterdiagnosesaremade.Anexpertreview panel, composed of clinicians from relevant specialties and patient advocacy, has discussed potential recommendations, and the formal Public HealthEngland reportwill be published in 2017.The Audit process is now embedded within the general NSHPC methodology for any newlyreported 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 datacollection is taking place.

DiscussionTheepidemiologyofHIV inpregnancy in theUKhas changed considerably since surveillance started.Today,only15%ofreportedpregnanciesare in women diagnosed during pregnancy, with a high proportion on cART at conception. In the context of the policy of treating all people livingwithHIVearly,thisproportionislikelytoincreaseinthefuture.ThenumberofbirthstoHIV-positivewomen 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 reflectsastabilizationinthenumberofsequentialpregnancies to women having subsequent pregnanciesafter their initialHIVdiagnosis. Theincreasing numbers of women aged over 40 years and of vertically-infected pregnant women are of note, given that these groups may be at increasedriskofadverseoutcomesand/orrequiremore 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%since2012-2014.Evenlowerriskofverticaltransmission 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 infantsborneachyearwhohavebeenexposedtoantiretroviral drugs for their entire gestation. Such “HIV-exposed uninfected” or HEU children arecurrently the focus of considerable interest from the research and policy communities with respect to potential impact of exposure to bothmaternalHIVandantiretroviraldrugsinfetalandearlylife.

Despite high uptake of antenatal testing and interventions to prevent MTCT, some infants are still acquiringHIV infectionperinatally or throughbreastfeeding.TheNSHPCauditofperinatalHIVinfections in children born from 2006, confirmedthat at least 60% of these (67/108) were bornto theminority ofwomenwithHIV infectionwhoremain undiagnosed at delivery. The audit has provided supplementary information to understand better the circumstances around transmissions that occur despite such low background MTCT rates.Themainreasonsidentifiedfortransmissionamongst undiagnosed women were declining antenatal HIV testing and seroconversion.Amongst diagnosed women, the main reasons identified were difficulties with adherence andlate 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 treatmentprior toarrival in theUKwhichreflectsimprovements in HIV diagnosis and treatmentcoverage 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(AdolescentsandAdultsLivingwith Perinatal HIV), a prospective cohort study,is built on the NSHPC and CHIPS surveillancestudies.AALPHIstartedrecruitmentattheendof2012, and by 2015 had enrolled over 300 young people livingwithHIVandabout100controls. Itaims to explore the impact of life-long HIV andlong-term antiretroviral therapy on neurocognitive, cardiacandmetabolicfunction,growth,andsexualand reproductive health (more details at www.ctu.mrc.uk ). The pregnancies now being reported in women themselves infected vertically highlight how theHIVepidemic in theUK ismaturingand thatongoing surveillance, research and collaboration is vital to capture and respond to ever changing needs.

AcknowledgementsDuring2016-17theNSHPCteamatICHincludedHelen 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.


Funding

This study is funded mainly from Public HealthEngland’s Centre for Infectious DiseaseSurveillance and Control, and NHS InfectiousDiseases in Pregnancy Screening (IDPS) programme(partofPHE);additionalsupporthascome from the collaborating institutions.

Public and patient engagementAvert.Web: https://www.avert.org

Body and Soul. Web: http://www.bodyandsoulcharity.org

Children’sHIVAssociation(CHIVA).Web: https://www.chiva.org.uk/

Positively UK.Web: http://www.positivelyuk.org

References1. Townsend CL, Cortina-Borja M, Peckham CS, Tookey PA. Trends in management and outcome of pregnancies in HIV-infected women in theUnited Kingdom and Ireland, 1990-2006. BJOG2008;115:1078-86

2. FrenchCE,Cortina-BorjaM,ThorneC,TookeyPA. Incidence, patterns, and predictors of repeat pregnancies among HIV-infected women in theUnitedKingdomand Ireland, 1990-2009. JAIDS2012;59:287-93

3. Townsend CL, Byrne L, Cortina-Borja M, Thorne C, de Ruiter A, Lyall H, et al. Earlierinitiation of ART and further decline in mother-to-

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. TownsendCL,deRuiterA,PetersH,Nelson-Piercy C, Tookey P, Thorne C. Pregnancies in olderwomenlivingwithHIVintheUKandIreland.HIVMed.2016Nov16

6. Peters H, Francis K, Judd A, Collins IJ andThorneC.Current trends inHIV-positivechildrenlivingintheUKandIreland.InSeattle,USA;2017

7. Peters H, Thorne C, Tookey PA, Byrne L.NationalauditofperinatalHIVinfectionsintheUK2006-2013: what lessons can be learnt? Submitted toHIVMedicine2017

Researcher contactsDr Claire Thorne, Population, Policy and Practice Programme,UCLGOSInstituteofChildHealth,30GuilfordSt,London,WC1N1EHTel:02079052604E-mail: [email protected]

HelenPeters,Population,PolicyandPracticeUnit,UCLGOSInstituteofChildHealth,30GuilfordStreet,London,WC1N1EH Tel:02079052693 Email:[email protected]

Co-investigators

UCLGOSInstituteofChildHealth:Dr Pat Tookey; Professor Mario Cortina-Borja


Nutritional Rickets presenting to secondary careKey points• 319 cases were notified, and 130questionnaires met the case definition.• Although a completely treatable condition, rickets continues to affect children in the UK.• Two deaths have occurred.

SummaryRickets 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 UKor,notexposingourselvestosunlight.

Children with darker skin e.g. African, Caribbean, AsianandMiddleEastern,thosewhoaregrowingrapidly (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.

Surveillance period

March2015-March2017(inclusive).

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

AnalysisOver25months(fromMarch2014toMarch2017)a total of 319 cases have been notified to theBPSU 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 childrenwere agedbetween5and12years11months (3.1%,n=4),with the least children aged between 13 and 16 years(1.5%,n=2).Thereweremoremales(70%,91/130) than females (30%, 39/130) presentingwith the condition. The two most common ethnic backgroundswereBlack/African/Caribbean/BlackBritish (44.6%, 58/130) and Asian/Asian British(40.8%,53/130).

Nutrition: Feeding practices were notified in 125cases and showed that most children were on solids (68.5%, 89/130) and only one child wasexclusively formula fed compared to 17.7%

Figure 8: Map of confirmed cases

Dr Priscilla Julies


Figure 9: Seasonal variation of presenting cases

(23/130) who were exclusively breastfed. Cow’smilk allergy/intolerence (7.7%, 10/130), irondeficiency (6.2%; 8/130) and eczema (6.2%,8/130)werethecommonestassociatedconditions.

Clinical presentation: Of the 130 included cases most children (86.9%, 113/130) presented withbony abnormalities, followed by radiological abnormalities(73.1%,95/130)andneuromuscularabnormalities (47.7%, 62/130). Of the 130cases , 24 children presented as a result of an incidental blood test or x-ray. Interestingly 15children presented with associated fractures (11.5%, 15/130).At the time of diagnosis 77.7%ofchildren(101/130)werenotreceivingvitaminDsupplements.

Discussion

The surveillance study provides us with detailed information on the current burden of nutritional rickets caused by vitamin D deficiency. Thecommonest risk factors captured by the clinical questionnaire include ethnicity, diet and allergies. It is also important to identify mothers with vitamin Ddeficiency,assupplementingtheirchildrenmayhelp in preventing rickets in their offspring.

Thecasedefinition for this study included25OHvitamin D <25nmol/L as a cut off and we foundthat, many hospitals had a range higher than this case definition. Thismay have impacted onthe number of cases notified to the BPSU. Theextended year has provided unique informationabout the clinical management of cases particularly around supplementation practices in the UK. In all, there was also good correlation, in performing

x-raysandbiochemistry toenableaccuratecaseascertainment.

Funding

ThisstudywassupportedbytheVitaminDMissionFund (now Nutricia) through an educational grant totheRoyalNationalOrthopaedicHospital.

References

1. HolickMF.Resurrectionofvitaminddeficiencyandrickets.JClinInvest.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 HospitalWatfordRd,HarrowHA13UJ

DrPriscilla Jules,Royal FreeHospital, PondSt,London NW3 2QGE-mail: [email protected]

Co-investigators

BirminghamChildren’sHospital:DrNickShawChildren’sUniversityHospital: Dr Ciara McDonnellRoyalManchesterChildren’sHospital: Professor Zulf MughalGreatOrmondStreetHospital:DrAlastairCalder UniversityHospitalGlasgow:DrHelenMcDivittRCPCH:KarinaPall,MarinaLeoniBPSU: Richard Lynn


Pierre Robin sequenceKey points• Surveillance has now ended, and a total of 197 cases were reported to the BPSU. Anadditional 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 ahightreatmentburden;89%requiredaperiodofnasogastrictubefeeding,and70%ofrequiredthe use of an airway adjunct which included tracheostomy insertion in 10%of cases.Theseinterventions are often required for many weeks or months. • 12-month outcome data is currently being collected

SummaryPierre 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 neonatalperiod 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, anartificialairwayadjunct,orsurgery.

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 heartfailure and neurodevelopmental problems.

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 periodJanuary2016-January2017(inclusive). Follow-up period: Follow-up questionnaire at 12 months after initial diagnosis, ending in January 2018.

MethodologyData 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

AnalysisOver the 13 month surveillance period a total of 245 case notifications, ofwhich 197 caseswerereported via the Orange ‘eCard’ and 48 were notifiedby regionalcleft teamsviaanalternativereportingcard.Eightcaseswerereportedinerrorordidnotmeetthecasedefinition,and62duplicatereports or questionnaires were received. At the time of writing clinical data has been submitted for 133confirmed(de-duplicated)cases,andafurther42 questionnaires are awaited. Infants were a

Dr Marie Wright

Figure 10: Sources of case reporting


medianof69daysoldatthetimeofquestionnairecompletion.

There was an equal gender distribution (males, n=66). The median gestational age at birth was 39+2weeks,andmedianbirthweightwas3200g(range 1030 – 4670g). 14 infants (10.5%) werebornpretermat<37completedweeks.Therewasonly one case of multiple pregnancy. Main ethnic groupsconsistedof85.7%white,Indian3.8%and3%Pakistan.

Diagnosis and antenatal history:75%ofmothershad a detailed antenatal ultrasound scan during pregnancy, but there was an antenatal suspicion ofPRSdiagnosisinonly19%ofcases(n=25).Themost common abnormalities seen on ultrasound were micrognathia (n=8) and polyhydramnios (n=7). Cleft palate was suspected antenatally in2cases.11%ofinfants(n=15)hadafirst-degreerelative with an orofacial cleft, of which over half had a diagnosis of Stickler Syndrome (n=8).

Presentation and initial management: 89% ofinfants(n=119)werediagnosedwithPRSwithin48hours of birth, and the diagnosis was made beyond thefirstweekoflifeinonlyfourcases.Mostinfantswere admitted to a neonatal (79%) or paediatricunit (15%) for observation and management,whilst 6% were discharged home directly fromthematernityward.42%ofinfantshadothernon-PRS associated congenital anomalies, including 10% who were suspected or confirmed to havean underlying genetic syndrome. No congenital anomalies were reported for 77 (57.9%). Minoranomalieswerereportedin21(15.8%)andmajorin22(16.5%).Geneticsyndromeswereconfirmedor suspected in 13 (9.8%) and includedStickler syndrome (n=3), Noonan syndrome, Smith-Magenis syndrome, Smith-Lemli-Opitz syndrome, Sotos syndrome, Poland syndrome, Congenital disorder of glycosylation (n=1) and chromosomal (n=4).

Airway management: Signs of upper airway obstruction(UAO)werepresentin86%ofinfants,and70%ofinfantsrequiredactivemanagementofUAO with an airway adjunct (Figure 11).

Feeding management: 99% of infants requiredfeeding support, either with specialised bottle feeding equipment (e.g. Haberman feeder, DrBrown 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 atmedian 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.

DiscussionPreliminary 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 orpaediatric 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 ofcasesand70%of infants requiredactive airwaysupport. Although the use of a nasopharyngeal airway (NPA) for UAO management appears to

Figure 11: Initial airway management in infants with PRS


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 engagementCleft 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 SickChildren’sHospitalforheradministrativesupport.We are also grateful to the Cleft and Craniofacial CSGoftheNIHRCRNfortheirinputintoourstudymethodology, case definition, and questionnairedesign, 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. VatlachS,MaasC,PoetsCF.Birthprevalenceand initial treatment of Robin sequence in Germany: a prospective epidemiologic study. OrphanetJRareDis.2014;9(9)

2. Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate CraniofacJ.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 contactsDr Marie WrightSpecialty registrar in Paediatric Respiratory Medicine,RoyalBromptonHospital,SydneyStreet, London, SW3 6NPTel:07906312371E-mail: [email protected]: [email protected]

Co-investigators

RoyalHospitalforSickChildren,Edinburgh: Dr Don Urquhart, Dr Felicity Mehendale, Dr PatriciaJackson(retired),DrEdileMurdoch OurLady’sChildren’sHospital,Dublin: Dr Sheila Javadpour


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 untilMay 2017 4,194 children have been notified;1,792childrenhaveaknowndiagnosisotherthanvCJD,withover190differentneurodegenerativedisorders in this diagnosed group. • Six cases of vCJDhave been reported tothestudysinceDecember1998;fourhavebeenclassified as “definite” and two “probable”; all have now died.• The National Creutzfeldt-Jakob Disease Research and Surveillance Unit in Edinburghreports that there have been 178 deaths fromdefinite or probable vCJD in UK patients of all ages. Until 2016 all these cases were methionine homozygous at codon 129 of the prion proteingene (PRNP). It is significant that the first and only confirmed methionine/valine heterozygousvCJD adult case was identified last year (2016).

SummaryActive 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 Creutzfeldt-Jakob Disease Research and Surveillance Unit in Edinburgh(NCJDRSU)andPublicHealthEngland.The study strategy is to look at the broad group of rare neurodegenerative disorders affecting children,carefullyexaminetheclinicaldetailsanddetermine 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

Methodology

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

Surveillance periodMay1997–April2022(inclusive)

Analysis

ByMay2017,4,194childrenhadbeennotified;190are still “under investigation” by their paediatricians; 1,916 did not meet the PIND definition, wereduplicateorerrornotificationsand71casesremainoutstanding.

Theremainingcaseswereclassifiedasfollows:

Definite and probable cases of vCJD:SixcasesofvCJD (fourdefiniteand twoprobable)havebeennotified - the youngestwas a girl aged 12 yearsat 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 nowdiedandneuropathologyhasconfirmedvCJDin four cases; a post-mortem was not carried out on the remaining two cases.

Children with PIND who have definite diagnoses other than vCJD:Morethan190distinctdisorderswere diagnosed in these 1,792 children. Inthe 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).

The PIND teamThePINDExpertGroup


Children with PIND and no underlying diagnosis (idiopathic group): The PIND Expert Groupmeet regularly to discuss this group of children, currently 219. If a “new” variant of vCJD shouldarise or if the paediatric presentation differed from the adult presentation, this group could include suchaphenotype.However,thereiscurrentlynoevidence of a “new” unrecognised disorder in this group.

DiscussionDuring 20 years of surveillance, six childrenpresenting with vCJD under 16 years of age have been notified to the study, including fourwith definite vCJD and twowith 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 oftransmission (particularly as the first confirmedadult 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 therelevant journals.

References1. Verity CM, Nicoll A, Will RG, Devereux G,StellitanoL.VariantCreutzfeldt-Jakobdisease inUK children: a national surveillance study. Lancet 2000;356:1224-7

2. DevereuxG,StellitanoL,VerityCM,NicollA,WillR.,RogersP.VariationsinneurodegenerativediseaseacrosstheUK:findingsfromthenationalstudy of Progressive Intellectual and Neurological Deterioration(PIND).ArchDisChild2004;89(1):8-12

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

3. Winstone AM, Stellitano L, Verity, CM.Niemann–Pick type C as a cause of progressive intellectual and neurological deterioration in childhood. Developmental Medicine & ChildNeurology2017;59:965-72

4. Peden AH, Head MW, Ritchie DL, BellJE, Ironside JW. Preclinical vCJD after bloodtransfusion in a PRNP codon 129 heterozygouspatient.Lancet2004;264:527-29

5. Mok T, Jaunmuktane Z, Joiner S, Campbell T et al.VariantCreutzfeldt–JakobDiseaseinaPatientwithHeterozygosityatPRNPCodon129.NEnglJMed2017;376:292-294

FundingDepartmentofHealthEngland [PR-ST-1216-10001]

Public and patient engagementCreutzfeldt-Jakob Disease Support Network. Web: http://www.cjdsupport.net

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 contactsDr CM Verity (Principal investigator), Professor A Nicoll, Professor R Will, Ms A Powell, Ms AM Winstone

MsA Powell, MsAMWinstone - c/o Children’sServices,Box267,Addenbrooke’sHospital,HillsRoad, Cambridge, CB2 0QQ Tel:01223216299/01223217598E-mail:[email protected] or [email protected]


Visual impairment and blindnessKey points• The study is progressing very well with excellentsupportfrompaediatricians• 183 case reports of children with severe visualimpairment/blindnesshavebeenconfirmed– this is in keeping with the number we anticipated through the British Paediatric Surveillance Unit and the British Ophthalmological Surveillance Unit.

SummaryMost children living in the UK with visual impairment or blindness are likely to be affected from birth or infancy and will experience a significant lifelongimpact on their development, education, social and emotional wellbeing. The aim of this second BritishChildhoodVisualImpairmentandBlindnessStudy (BCVIS2) is to determine the incidence,causes, mode/context of detection, associatedfactors, management and short-term health and social outcomes of all-cause childhood visual disability.All children aged ≤18 years diagnosedduring a one year period as being severely visuallyimpairedorblindwillbeidentifiedthroughtheir clinicians using national active surveillance independently but concurrently through the British Paediatric Surveillance Unit and the British Ophthalmological Surveillance Unit (BOSU). Therewill be simultaneous identification of thosechildren 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 willinform 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 anevidence 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 assevere visual impairment and blindness (SVI/BL); details of the study protocol are available at h t t p : / / w w w . r c p c h . a c . u k / b p s u / b c v i s

Surveillance period

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

Analysis

Thusfar,349caseshavebeenreportedofwhich183havesofarbeenconfirmed.Afurther279werereported through BOSU. Preliminary descriptive analyses on the BPSU cohort is highlighted below.

120 (66%) children were diagnosed with poorvision consistent with SVI/BL before their firstbirthday (Table7). Children from ethnic minorities (non-white) and those in the lowest socioeconomic group (bottom quintile) are over-represented in SVI/BL (32%and29%respectively)compared tothe general UK population.

ComparedtothegeneralUKchildpopulation,SVI/BL children are more likely to be born premature (<37weeks,26%)andbornlowbirthweight(<2.5kg,23%). The factors operating in the prenatal orperinatalperiodwereresponsibleforSVI/BLin60%(n=109)and14%(n=26)ofcasesrespectively,with12%(n=22)ofcaseshavinganunknownaetiologybut thought to be pre- or perinatal e.g. congenital abnormalities.14%(n=25)ofcaseswerecausedby a factor operating in childhood. The majority of children had an additional major non-ophthalmic disorderor impairment (87%,n=181). In termsoftheprimarydisordersleadingtoSVI/BL,themostfrequent was cerebral visual impairment (CVI,

Figure 14: Reporting sources for SVI/BL confirmed reports

Table 7: Age at diagnosis of SVI/BL

Age diagnosed with poor vision n %<1 year 120 661-4 years 18 105-14 years 17 915 years 2 1Unknown 25 14

Professor Jugnoo Rahi


56%), following by optic nerve hypoplasia (18%)andretinaldetachment(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, withthe majority caused by factors operating in the prenatal and perinatal period. SVI/BL childrenwere significantly more likely to be from anethnic 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 largestprimarydisorderresultinginSVI/BL.

The findings will provide the evidence base foradvocacy 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, particularlyby 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

toidentifymodifiableriskfactors.Additionally,thisstudy 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

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

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

Researcher contactsProfessor Jugnoo Rahi, Population, Policy and PracticeUnit,UCLGOSInstituteofChildHealth,30GuilfordStreet,London,WC1N1EHTel:02079052250E-mail: [email protected]

Twitter: @bcvistudy

Co-investigators

UCLGOSInstituteofChildHealth:Lola Ameenat Solebo, Phillippa Cumberland, Lucie Teoh GreatOrmondStreetHospital: Dr Jenefer Sargent

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


Appendix - Publications 2016 -2017

Acute infectious hepatitis1. 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-2016-311916https://www.ncbi.nlm.nih.gov/pubmed/28377449

Acute pancreatitis

2.MajbarAA,CusickE,JohnsonP,LynnRM,HuntLP, 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 syphilis3. Simms I,TookeyPA,GohBT, Lyall H, EvansB,TownsendCL,FiferH, IsonC.The incidenceof congenital syphilis in the United Kingdom: February 2010 to January 2015. BJOG. 2016 Mar 2. doi: 10.1111/1471-0528.13950. [Epubahead of print] https://www.ncbi.nlm.nih.gov/pubmed/26931054

Early onset eating disorders4. Pinhas L, Nicholls D, Crosby RD, Morris A, LynnRM,Classificationofchildhoodonseteatingdisorders: A latent class analysis. Madden Int J EatDisord.2017Jan20.doi:10.1002/eat.22666.[Epubaheadofprint]https://www.ncbi.nlm.nih.gov/pubmed/28106914

HIV infection & perinatal HIV exposure5. Raffe S, Curtis H, Tookey PA, Peters H,Freedman A, Gilleece Y and on behalf of the BritishHIVAssociationAuditandStandardsSub-Committee. UK national clinical audit: management ofpregnanciesinwomenwithHIV.BMCInfectiousDiseases. 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

7. FrenchCE,ThorneC, Byrne L, Cortina-BorjaM, 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):161-170

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

9.TownsendCL,deRuiterA,PetersH,Nelson-Piercy C, Tookey PA, Thorne C. Pregnancies in olderwomenlivingwithHIVintheUKandIreland.HIVMed. 2017Aug;18(7):507-512. doi: 10.1111/hiv.12469. https://www.ncbi.nlm.nih.gov/pubmed/27862854

10. Thorne C, Tookey PA. Strategies for MonitoringOutcomes inHIV-ExposedUninfectedChildren 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/ritonavirduring pregnancy: analysis of population-based surveillancedatafromthenationalstudyofHIVinpregnancy 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, TownsendCL. Duration of ruptured membranes and mother-to-child HIV transmission: a prospectivepopulation-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 prospectivepopulation-based cohort study Archives of Disease in Childhood Published Online First: 29 March2017.doi:10.1136/archdischild-2016-312238

Intussusception14. 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 deterioration15. Winstone AM, Stellitano L, Verity, CM.Niemann–Pick type C as a cause of progressive intellectual and neurological deterioration in childhood.DevMedChildNeurol.2017Jun2.doi:10.1111/dmcn.13476. https://www.ncbi.nlm.nih.gov/pubmed/28574146

16. Stellitano LA, Winstone AM, van der Knaap MS, Verity C. Leukodystrophies and geneticleukoencephalopathies 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


Appendix - Presentations 2016 -2017

Bacterial meningitis in Infants aged <90 days

1. Okike I, Ladhani S, Johnson A, HendersonK, 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. ESPIDconference,BrightonUKMay10-152016

2. Ladhani S. Epidemiology of MeningococcalDisease in the UK. ESPID conference, BrightonUK, 10-15 May 2016

Behcet’s syndrome

3.PainC,RiceH,BeresfordM,BroganP,FortuneF,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 inUKand Irish infants younger than90days, 2014-2015. RCPCH conference LiverpoolUK April 2016

7.O’SullivanC,LamagniT,PatelD,EfstratiouA,Reynolds A, Cunney R, Meehan M, Campbell R, Doherty L, BoyleM,Davies E, Heath P. GroupB Streptococcal (GBS) Disease in UK and Irish InfantsYoungerThan90DaysOfAgeIn2014-15.ESPIDconference,BrightonUK,May10-152016

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 deterioration9. Verity C. Responding to public healthemergencies / addressing emerging infectiousdisease–PIND-H1N1;newvaccines.BPSU30thanniversary symposium, RCPCH conference,Liverpool UK April 2016

10. Verity C. Leukodystrophies and geneticleukoencephalopathies in childhood - a national epidemiological study. British Paediatric Neurology Association Meeting, Sheffield UK. 27-29 January 2016

11. Winstone AM. Children with Niemann-Pick Type C disease in the UK – review of the clinical spectrum in 53 children. British Paediatric NeurologyAssociationMeeting,SheffieldUK.27-29thJanuary2016

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.AbstractpresentedatRCPCHconference Liverpool UK April 2016

Nutritional Rickets

13.JuliesP.Vitaminddeficiency– theevidenceto date – BPSU 30th anniversary symposium, RCPCHconference,LiverpoolUKApril2016

Exchange blood transfusion

14. Gottstein R. Rennie J et al. Oral presentation of interim data analysis at regional meeting: North-West Neonatal Study Day; Manchester, January 2016.

15. Gottstein R. Rennie J et al. Poster presentation at 17th Annual NATA Symposium; Dublin, April2016TransfusionMedicine2016;26(Suppl1):39

16. Gottstein R. Rennie J et al. Poster presentation atRoyalCollegeofPaediatricsandChildHealth(RCPCH) annual conference; Liverpool, April2016. Arch Dis Child 101(Suppl 1):A254-A255 · April 2016

17. Gottstein R. Invited oral presentation atBritish Blood Transfusion Society (BBTS) annual Conference;Harrogate,UK,September2016

18. Gottstein R. Rennie J et al. Poster presentation attheEuropeanAssociationofPaediatricSocieties(EAPS)Conference,GenevaOctober2016

Congenital Zika syndrome

19.OeserC.CongenitalZikaSyndrome:Obstetricand paediatric surveillance in the UK and ROI. Poster, International Meeting on EmergingDiseasesandSurveillance,Vienna,11/2016

20. Oeser C. BPSU surveillance of congenital Zika syndrome,Presentation,9thInternationalNetworkof Paediatric Surveillance Units (INOPSU) ScientificMeetingVancouver,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 surveillanceintheUKandROI.Poster,PHEannualconference,Warwick,09/2016


Notes

Dr Richard Reading ChairDr Rachel Knowles* Medical Advisor (non-infectious disease), UCL Great Ormond Street Institute of Child HealthDr Olivier le Polain de Waroux** Medical Advisor (infectious disease), Public Health England

Medical Advisor (non-infectious disease), UCL Great Ormond Street Institute of Child HealthScientific CoordinatorRoyal College of Physicians of IrelandDirector of Research and Policy. Royal College of Paediatrics & Child HealthVice President Science & Research, Royal College of Paediatrics & Child HealthConsultant in NeonatologyConsultant PaediatricianConsultant in Intensive CareSenior Epidemiologist, Health Protection ScotlandGeneral PaediatricsConsultant in NephrologyPatient and Carers RepresentativeSpecialist Registrar in Paediatric Infectious Diseases & ImmunologyPatient and Carers RepresentativeConsultant in Public Health Medicine

Dr Jamie Lopez Bernal Mr Richard Lynn Dr Robert Cunney Ms Jacqueline Fitzgerald Professor Anne Greenough Dr Kathryn Johnson Dr Simon Lenton Dr Simon Nadel Dr Kevin Pollock Professor Alastair Sutcliffe Dr Mohan Shenoy** Dr Jane Sutton Dr Marc Tebruegge Mrs Madeleine Wang Dr Rachael Wood Dr Dominik Zenner Public Health England

* Stepped down in 2016** Stepped down in 2017

Membership of Scientific Committee 2016

British Paediatric Surveillance Unit

Published October 2017 by the British Paediatric Surveillance Unit:Royal College of Paediatrics and Child Health5-11 Theobalds RoadLondon WC1X 8SH

Telephone: +44 (0) 207 092 6173/74E-mail: [email protected]: http://www.rcpch.ac.uk/bpsuTwitter: @BPSUTweet

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