Screening in Developmental Dysplasia of the Hip (DDH) King James IV Professorial Lecture, 15th. September 2016, British Orthopaedic Association Congress, Belfast Robin W Paton PhD, FRCS (Orthopaedic) No conflicts of interest

King James IV of Scotland

The little red book CDH/DDH Screening policy in the UK from 1969 to 2004 ‘60% of CDH have risk factors’

There is your baby referred with a hip problem There is the ultrasound machine Sister Kath Eccles 1991

Screening in DDH: US Preventative Services Task Force, 2006 An effective screening programme must identify the cases of DDH earlier than would have been identified in the usual course of care and must lead to better functional outcomes than late treatment. Any benefits should outweigh the harms of screening. US Preventative Services Task Force, 2006

The ‘Ideal’ Screening Programme Applied to DDH The condition should be important * Examination and or treatment are/is acceptable to the patient * Continuously rolled out and repeated (audit) * Treatment and diagnostic facilities should be available * There should be an effective and accepted treatment Recognisable latent and early symptomatic stage should be present Opinions on who should be treated are agreed The natural history of the condition should be known Guaranteed safety, sensitivity and specificity of the test (ideally >90%) Tests are inexpensive and simple Cost effective programme Wilson & Jungner, WHO 1968

What is DDH? Developmental dysplasia of the hip: A dynamic condition in which the hip joint abnormality may improve or deteriorate with growth Klisic 1989 Neuromuscular, neurological, syndromal and skeletal dysplasias are excluded Bialik et al 1999 Homer et al 2000

The spectrum of presentation in DDH: Klisic 1989 Dysplasia Reducible subluxation/dislocation Irreducible dislocation

What is the outcome measure: ‘pathological’ DDH? Traditionally this is the incidence of irreducible dislocation of the hip Macnicol 1990

What is pathological DDH in the neonate? Clinical instability (Ortolani/Barlow): spontaneously resolve in 70 to 90% Barlow 1962, Gardiner & Dunn 1990, Sonographic DDH: Graf Type II 90% resolve spontaneously Graf Type III unknown, < 25% spontaneously resolve Graf Type IV < 90% may resolve Castelein et al 1992, Sampath et al 2003, Rosendahl & Toma 2007, Wood et al 2000 Andersson & Funnemark 1995

Screening in DDH Clinical screening: Neonatal (universal) General Practitioner/ HCP (universal) Sonographic imaging: Selective ‘at risk’ Universal (neonatal)

Clinical hip screening: Ortolani manoeuvre: 60% sensitive & 100% specific Barlow manoeuvre: PPV = 22% Jones 1977, 1998 Patel 2001 Barlow & Ortolani manoeuvres failed to identify 66.7% of those hips that required subsequent surgical intervention Robinson 1998

Clinical hip screening: Effectiveness of clinical hip screening in UK & USA disputed Dezateux 2000 Hall & Elliman 2003 Shipman et al 2006 Lehmann et al 2000 Not as effective as Swedish model Duppe & Danielsson 2002

Clinical hip screening: ‘Late’ or overall irreducible hip dislocation rates: Andren &Von Rosen (1958) 0.07 per 1000* Hadlow (1988) 0.10 per 1000 Myers et al (2009) 0.29 per 1000 Duppe & Danielsson (2002) 0.07 to 0.51 per 1000* Hoaglund et al (1981) 0.1 per 1000 Macnicol (1990) 0.5 per 1000 (UK) Overall surgical intervention rate in the UK: Godward & Dezateux (1998) 0.78 per 1000

Literature review of Screening (Ultrasound & Clinical) in DDH: Insufficient evidence to give clear recommendations (Cochrane review 2013) Levels of evidence generally poor Conclusions guarded (no improvement in late diagnosed DDH requiring surgery)

AAOS recommendations 2014 Moderate evidence to reject universal ultrasound screening Moderate evidence to undertake an imaging study < 6 months of age (FH, Breech or history clinical instability)

Hip screening policy in England: NIPE guidelines 2008 Ortolani & Barlow manoeuvres < 72 hrs. Ultrasound imaging of hip if abnormal < 2 weeks expert opinion within 3 - 4 weeks * ‘at risk’ hips (Breech & FH) ultrasound imaging of hip < 6 weeks expert opinion 6 - 8 weeks * General Practitioner/ Health Care Professional assessment at 6 - 8 weeks

Public Health England NIPE 2016: ‘Screen positive signs’ (6 -8 weeks) Difficulty in abducting hips to 90 degrees * Asymmetry of skin folds (buttocks & posterior thighs) * ‘Clunk’ on the Ortolani/Barlow manoeuvre Galeazzi positive (short leg)

International guidelines for DDH screening No Internationally agreed standards: Austria & Germany: universal sonographic hip screening Switzerland* universal sonographic hip screening (abandoned in 2004) Norway & France selective ‘at risk’ hip screening USA breech & FH in females, breech in male Canada clinical hip screening Hong Kong clinical screening & selective ultrasound Rosendahl & Toma 2007 Dorn & Neumann 2005 Lehmann et al 2000, Patel 2001 Shipman et al 2006 Tong et al 2011

Comparison between clinical,selective & universal sonographic hip screening in DDH No statistical difference in outcome measures between: Clinical (universal) Clinical (universal) & selective U/S hip screening Clinical (universal) & universal U/S hip screening Holen et al 2002 Rosendahl et al 1996

Problems with ultrasound imaging in DDH Numerous classification systems with lack of validation and subjective analysis elements Operative dependant: variable Kappa scores (intra- and inter observer error) The natural history of sonographic hip instability and dysplasia has not been defined Roposch et al 2006 Dias et al 1993 Rosendahl et al 2007

Sonographic abnormalities a driver of over diagnosis in DDH? ‘Ability to detect smaller abnormalities axiomatically tends to increase the prevalence of any given disease’ Black 1998 Black 1998

Current hip screening pathways in the UK: Three main screening arms: Neonatal clinical hip screening Selective ‘at risk’ sonographic screening General Practitioner 6 to 8 week clinical ‘hip check

Hip Screening in DDH ‘Does selective ultrasound imaging of ‘at risk hips’ and clinically unstable hips , in Developmental Dysplasia of the Hip produce an effective screening programme?’ PhD Thesis, University of Lancaster, 2011 A prognostic level I b, evidence based study

Algorithm on primary clinical screening (neonatal) Total population (Clinically screened at birth by paediatric dept.) 37,510 118 referred as clinically unstable (0.31%) 85 clinically stable (false + clinical) 33 clinically unstable positive O/B (true + clinical) 80 unstable on U/S (true + U/S) 38 TI,II,III (false + U/S) 2 irreducible hip dislocations

Secondary ‘at risk factors’ Algorithm on secondary screening ‘at risk’ hips pure risk factors 2389 (6.37%)* Total population 37,510 Secondary ‘at risk factors’ (including clicks 129) 2826 (7.53%) 7 subluxable/ dislocatable true + 23 Graf Type III true + 5 irreducible true +

37,392 births checked in GP clinical assessment Algorithm on General Practitioner 6 week clinical hip check (6 to 12 weeks) 37,392 births checked in GP clinical assessment 2 clinically unstable (O/B +) true + 41 false + 13 false - 37,336 true -

37,392 births checked in GP clinical assessment Algorithm on General Practitioner 6 week clinical hip check (6 to 12 weeks) 37,392 births checked in GP clinical assessment 2 clinically unstable (O/B +) true + 41 false + 13 false - 37,336 true -

Statistical analysis of screening pathways Referral pattern and statistics for DDH (figures in brackets identify ‘at risk’ if Graf Type III hips considered as not pathological and therefore FP)   Primary neonatal screening (Clinical) Primary neonatal screening (US) ‘At risk’ hip screening GP screening 6 week check (Clinical) Sensitivity 66% 72.07% 100% 13.34% Specificity 99.77% 99.90% 94.22% (93.3%) 99.9% PPV 27.97% 67.8% 20.47% (7.02%) 4.65% NPV 99.95% 99.92% 99.96%

  At risk’ pathological DDH: referrals for clinically unstable hips removed Adequate power analysis in Breech & FH ‘Risk’ factors Gender Number referrals Graf Type Incidence III IV Irreducible Total Breech Male 594 1 - 1:594   Female 760 16 6 2 24 1:32 FH 198 1:99 4 7 1:28 CTCV 26 52 1:52

95% Confidence Intervals of the mean in ‘risk factors’ 95% CI ‘tight’ CTEV CTCV breech 95% CI ‘wide’ Strong family history oligohydramios postural TEV

Power analysis in ‘risk factors’ Adequate power analysis Breech strong family history CTCV gender (clinical instability removed)

‘Risk factors’ referred Inadequate power analysis (low numbers) Graf Type II Graf Type III Graf Type IV Irreducible CTEV n = 52 - TEV n = 405 1 Oligohydramnios n = 198 Clicky Hip n = 129

Further research projects: 10 to 21 prospective observational longitudinal studies

Is Limited abduction of the hip a useful clinical sign in the diagnosis if developmental dysplasia of the hip? Q Choudry, R Goyal, R W Paton, Arch Dis Child 2013 LHA < 20 degrees considered positive 37518 births 2876 neonates & infants screened 492 patients limitation of abduction 55 patients unilateral LHA

Is Limited abduction of the hip a useful clinical sign in the diagnosis if developmental dysplasia of the hip? Unilateral LHA = PPV 40% compared with bilateral LHA = PPV 0.3% >8 weeks of age: unilateral LHA sensitivity = 78.3% PPV = 54.7% (Graf Types III, IV and irreducible hip dislocation) Time dependent association with unilateral LHA & pathological DDH

Asymmetrical Skin Creases (ASC), 21 year review Anderton & Paton 2016 Controversial if ASC significant Palmen 1961, Barlow 1962, Shipman 2006 73% of ASC isolated finding with normal hips clinically and sonographically Sensitivity & PPV = 0.0% Specificity = 100% 2.3% associated with significant hip pathology (2 unilateral LHA & LLD referred at 3 & 10 months) Conclusion: Isolated ASC not associated with significant hip pathology

Screening of selective ‘at risk’ factors in DDH an observational study CL Talbot RW Paton, Arch Dis Child 2013 Numbers referred & gender Graf Type III Graf Type IV Irreducible Total Incidence Breech (male) 982 - 0.0 Breech (female) 1209 19 8 3 30 0.025 FH (male) 348 FH (female) 373 2 6 5 1 12 0.006 0.032 Br & FH (male) 30 0.067 Br & FH (female) 42 0.071

Screening of selective ‘at risk’ factors in DDH an observational study 1360 males: 4 Graf Type III hips, incidence = 0.003 1624 females: 45 pathological hips, incidence = 0.028 Conclusion: Gender difference in incidence statistically significant p<0.001

Neonatal clinical hip screening in DDH: a 15 year prospective longitudinal study J Mace & RW Paton, BJJ 2015 201 cases referred at a mean of 1.62 weeks (95% CI 1.35 – 1.89) 48 clinically unstable hips diagnosed at the Paediatric Orthopaedic Clinic Referral Type Sensitivity Specificity PPV Clinical examination 62 99.76 24 percent Sonographic imaging 77 99.84 49

Neonatal clinical hip screening in DDH: A 15 year prospective longitudinal study 74% of Graf Type IV hips female (40/48) 6 female cases of clinical instability progressed to irreducibility (despite Pavlik harness) 94.4% of the irreducible hips requiring open or closed reduction were female (36 in 15 years) Majority of irreducible hip dislocation (DDH) are not identified in the neonatal instability referral group

Evaluation of the 6-8 week GP check for DDH: A 15 year study Davies R Evaluation of the 6-8 week GP check for DDH: A 15 year study Davies R., Mace J, Talbot C, Paton RW. Presentation BSCOS 2016 64,600 births 176 GP referrals to specialist Paediatric Orthopaedic Clinic (one stop) 5 unstable/ irreducible hips diagnosed clinically/ sonographically 13 screening failures (presented with irreducible hip dislocation later)

Evaluation of the 6-8 week GP check for DDH: A 15 year study Sensitivity 28% Specificity 99.7% PPV 2.8% Conclusions: 6-8 week GP screening check insufficient as a screening test 58% of late presenting irreducible hip dislocation not identified by: neonatal selective ‘at risk’ GP hip check

Is congenital talipes equino-varus (CTEV) a risk factor for pathological dysplasia of the the hip? A 21 year prospective, longitudinal observational study. RW Paton, Q Choudry et al, BJJ 2014 199 feet Type I Type II Type III Type IV Harold & Walker classification 43 51 105 N/A Graf Classification 259 18 (4 bilateral) 1 (resolved) - Conclusion: No significant link with idiopathic CTEV & pathological DDH

Screening in DDH: Conclusions: Surveillance not screening Sonographic selective screening of all ‘at risk’ hips has not reduced the rate of ‘late’ presenting irreducible dislocation The 6 week General Practitioner hip screening test is ineffective in its present form. Spontaneous resolution of clinical and sonographic abnormalities makes the diagnosis of ‘pathological’ hip dysplasia difficult. Neonatal abnormalities a poor outcome measure.

DDH a female disease. Most males are not ‘truly’ at risk if clinically stable. 7. Previously accepted risk factors are not ‘at risk’: CTEV Postural TEV oligohydramnios Caesarean section IUGR miscellaneous foot problems isolated asymmetrical skin creases clicks

Thank you: parents & children my family & colleagues

Genetics in DDH Acetabular dysplasia: Polygenetic environmental factors Joint instability: female Wynne Davies 1970

True pathology in DDH: Natural history in adults Irreducible hip dislocation/ acetabular dysplasia with subluxation Dysplasia 1-8% population Symptomatic OA females: age & dysplasia males: dysplasia THR in dysplasia obesity Presence of dysplasia does not = OA or THR Tonnis 1987 Wedge & Wasylenko 1979 Gent & Clarke 2004 Jacobson 2005/2006 Cooperman et al 1983

Male vs. female in DDH: birth population 37,510 ♀/♂ Dysplasia & Dislocation   TII ♀ ♂ TIII ♀ ♂ TIV ♀ ♂ IRREDUCIBLE 1997 4 6 1 2 3 1998 1999 2000 5 2001 9 11 2002 13 12 2003 19 7 2004 17 8 2005 18 20 2006 14 TOTAL 110 60 26 68 24 170 30 92 % FEMALE TYPE II 64.7% TYPE III 86.67% TYPE IV 73.91% IRRED. 94.74%

DDH: overall results SCREENING Irreducible Hip Dislocation Graf Type IV (dislocatable) (subluxable) Graf Type III Primary clinical 2 74 4 At risk 5 1 6 23 General Practitioner 11 (1 referred as unstable) 2 (both referred as unstable) 3 (1 referred as unstable) Late Paediatric 1 (initially TIII) TOTAL 19 77 15 26

DDH: Graf U/S hip abnormalities Birth cohort 37,510 (brackets = progression) Graf Classification Type II Type III Type IV Irreducible Number 170 (+19) 30 (+1) 92 (+3) 19 Incidence (per 1000) 4.53 0.79 2.45 0.51 Progressed 19 (13 III, 6 IV) 1 (irreducible) 3 (irreducible)   Resolved 170 (89.9%) 30 (96.8%) 92 (96.8%)

Problems with ultrasound imaging Many of the classifications are complex with subjective elements Graf, Morin & Harcke/Clarke The natural history of ‘abnormal’ sonographic hip instability and dysplasia has not been defined (no controlled trial between treated and non treated) A wide range of ‘pathological’ hips treated in the literature (0.18% to 7%) Andersson & Funnemark 1995 Bialik et al 1999 Von Kries et al 2003

Selective ‘at risk’ sonographic hip screening Advantages Can result in low splintage rates (0.18 to 0.3%) Andersson & Funnemark 1995 Sampath et al, 2003 Can reduce the need for diagnostic arthrograms McEvoy & Paton 1997

Selective ‘at risk’ sonographic hip screening Disadvantages: 18 – 31% dislocated/ dislocatable hips in ‘at risk’ groups. Only family history and breech presentation may be important (female) Kamath et al, 2007 Paton et al, 1999, 2005, 2011, 2014 Lehmann 2000 The rate of detection of ‘late’/ irreducible dislocation may be no better than the best clinical screening programs Macnicol 1990 Paton et al, 1999, 2005, 2011 Rosendahl et al 1994 Hernandez et al 1994

Universal sonographic hip screening Advantages: Appealing concept All potential cases of DDH imaged Early diagnosis & treatment Disadvantages: Expensive & time consuming Potential for over treatment (5 - 7% birth population) Skilled radiographer team and leadership required Compliance (85 – 90%) Bache et al 2002 Wirth et al 2002 Von Kries et al 2003

Graf classification for statistically significant ‘risk factors   Number referrals Graf classification Type I Type II Type III Type IV Irreducible Breech 1374 1256 76 17 21 2 FH 409 352 36 6 13 CTCV 83 66 11 5 1

Embryology & histology of the developing hip Femoral head and acetabulum develop from same mesenchymal cells. 6 to 7th week of intra-uterine life, a cleft develops, separating the future femoral head and acetabulum. 11th week the hip joint is fully formed Weinstein et al 2003, Watanabe 1974, Rooker 1979 The potential to dislocate the hip joint in the last 4 weeks of gestation is probably due to the decrease in femoral head cover

Further research studies in DDH Limited abduction of the hip 10 year prospective longitudinal study Neonatal hip instability: 15 year prospective longitudinal study

Further observational longitudinal studies Breech & FH ‘at risk’ : 15 year prospective longitudinal study CTEV: association with DDH: 21 year prospective study Evaluation of the 6-8 week GP 15 year prospective longitudinal study check for DDH

Complex sonographic classification systems: Complex with subject elements Graf Terjesan/Clarke/Morin

Guidelines on ultrasound imaging’s role in the diagnosis & treatment of DDH The case for ‘universal’ or ‘at risk’ ultrasound hip screening is not proven. Ultrasound should be used to confirm clinically diagnosed hip instability Ultrasound should be used to monitor treatment. Shipman et al 2006 Patel 2001 Lehmann et al 2000 Paton 2005

Inclusion & exclusion criteria INCLUSION CRITERIA: EXCLUSION CRITERIA: clinical instability 1. family history of ‘clicky hips 2. certain ‘risk factors’ 2. family history of ‘double nappies’ (FH, breech, oligohydramnios 3. Certain ‘risk factors’ postural TEV, CTEV, CTCV, MA) (IUGR, Caesarian section, miscellaneous foot) ‘pathological dysplasia / dislocation (U/S) 4. Radiological dysplasia (adolescent & adult) irreducible dislocation, infant (radiological) 5. neuromuscular dislocation unilateral limitation of the hip 6. syndromal dislocation age (if U/S imaging possible) 7. neonates/ infants born outside district ‘clicky’ hips (not on instability proforma) 8. FTA cases 9. primiparity/ maternal age 10. weight at gestation 11. follow up of normal Graf Type I hips 12. follow up to skeletal maturity 13. assessment of first born 14. asymmetrical skin creases 15. twins (assessment sibling)

Historical risk factors ‘risk factors’ (referred as risk factor) CTEV n=52: no Graf Type III, IV or irreducible hips TEV n=405 1 Graf Type III & I Graf Type IV hip 1:202 Oligohydramnios n=198 1 Graf Type III 1:198 Clicky hips n=129 1 Graf Type III

Is congenital talipes equino-varus (CTEV) a risk factor for pathological dysplasia of the the hip? A 21 year prospective, longitudinal observational study. Harrold & Walker classification: 43 Type 1, 51 Type 2 & 105 Type 3 Songraphic imaging: 259 Graf Type 1, 18 Graf Type 2 (4 Bilateral) 1 pathological hip: male Graf Type III hip resolved spontaneously without treatment. Conclusion: No significant link with idiopathic CTEV & pathological DDH

What is pathological DDH? Clinical instability spontaneously resolves in 70 to 90% Barlow 1962, Gardiner & Dunn 1990, Sonographic DDH: Graf Type II 90% resolve spontaneously Graf Type III unknown, < 25% spontaneously resolve Graf Type IV < 90% may resolve Castelein et al 1992, Sampath et al 2003, Rosendahl & Toma 2007, Wood et al 2000 Andersson & Funnemark 1995