Timing of Primary Surgery for Cleft Palate

doi:10.1056/NEJMoa2215162

Randomized Controlled Trial

. 2023 Aug 31;389(9):795-807.

doi: 10.1056/NEJMoa2215162.

Timing of Primary Surgery for Cleft Palate

Carrol Gamble¹, Christina Persson¹, Elisabeth Willadsen¹, Liz Albery¹, Helene Soegaard Andersen¹, Melissa Zattoni Antoneli¹, Malin Appelqvist¹, Ragnhild Aukner¹, Pia Bodling¹, Melanie Bowden¹, Karin Brunnegård¹, Gillian Cairns¹, Samantha Calladine¹, Linsay Campbell¹, Jill Clayton-Smith¹, Rachael Cooper¹, Elizabeth Conroy¹, Ahmed El-Angbawi¹, Berit Kildegaard Emborg¹, Josefin Enfält Wikman¹, Beth Fitzpatrick¹, Ana Paula Fukushiro¹, Cristina Guedes de Azevedo Bento Gonçalves¹, Christina Havstam¹, Anne Katherine Hvistendahl¹, Line Dahl Jorgensen¹, Kristina Klinto¹, Marit Berntsen Kvinnsland¹, Catriona Larham¹, Jorunn Lemvik¹, Louise Leturgie¹, Eva Liljerehn¹, Natalie Lodge¹, Anette Lohmander¹, Siobhan McMahon¹, Felicity Mehendale¹, Haline Coracine Miguel¹, Marianne Moe¹, Joan Bogh Nielsen¹, Jill Nyberg¹, Nina-Helen Pedersen¹, Ginette Phippen¹, Silvia Helena Alvarez Piazentin-Penna¹, Kathryn Patrick¹, Lindsay Pliskin¹, Lucy Rigby¹, Gunvor Semb¹, Lucy Southby¹, Maria Sporre¹, Ann-Sofie Björkman Taleman¹, Jorid Tangstad¹, Inge Elly Kiemle Trindade¹, Imogen Underwood¹, Stephanie van Eeden¹, Liisi Raud Westberg¹, Paula Ruth Williamson¹, Renata Paciello Yamashita¹, Kevin Munro¹, Tanya Walsh¹, William Shaw¹; TOPS Study Group

Collaborators, Affiliations

Collaborators

TOPS Study Group:
H F Aguiar, L Albery, H S Andersen, M Z Antoneli, M Appelqvist, R Aukner, A Aziz, M Becker, C E Bertier, P Bodling, S Boljanovic, M Bowden, Tvs Brosco, K Brunnegård, M Cadier, G Cairns, J Cajander, S Calladine, L Campbell, L Carney-Venters, J Clayton-Smith, R Cooper, E Conroy, M Devlin, A El-Angbawi, B K Emborg, J Enfält Wikman, P Eyres, H Extence, C Filip, B Fitzpatrick, A P Fukushiro, C Gamble, Cgab Gonçalves, M Hakelius, C Havstam, P Hodgkinson, A K Hvistendahl, L D Jorgensen, J C Jorge, L Kane, K Klinto, M B Kvinnsland, C Larham, J Lemvik, L Leturgie, E Liljerehn, N Lodge, A Lohmander, S McMahon, A Marcusson, H Mark, F Mehendale, N Mercer, H C Miguel, M Moe, T Moitt, J Mooney, M Mulki, K J Munro, E Neovius, J B Nielsen, L Norman, J Nyberg, N-H Pedersen, C Persson, G Phippen, Sha Piazentin-Penna, K Patrick, L Pliskin, L Rigby, P Rorison, G Semb, R Slator, L Southby, M Sporre, W Shaw, A Smyth, M C Swan, A-Sb Taleman, J Tangstad, P Tate, Iek Trindade, Iek Underwood, S van Eeden, H Vindenes, T Walsh, D Weichart, L R Westberg, D Whitby, E Willadsen, P R Williamson, R P Yamashita

Affiliation

¹ From the University of Liverpool (C.G., R.C., E.C., L.P., P.R.W.) and Alder Hey Children's NHS Foundation Trust (S.M.), Liverpool, Royal Hospital for Sick Children (G.C., N.L.) and the University of Edinburgh (F.M.), Edinburgh, Northern and Yorkshire Regional Cleft Lip and Palate Service (S.C.) and Leeds General Infirmary (C.L.), Leeds, Cleft Care Scotland, Glasgow (L.C.), Bristol Dental Hospital, Bristol (L.A.), the University of Manchester (J.C.-S., A.E.-A., G.S., K.M., T.W., W.S.) and Manchester University NHS Foundation Trust (M.B., K.P.), Manchester, Birmingham Children's Hospital (B.F.) and Birmingham Women's and Children's NHS Foundation Trust (I.U.), Birmingham, Salisbury District Hospital, Salisbury (G.P.), Royal Victoria Infirmary, Newcastle upon Tyne (L.R., S.E.), and Oxford University Hospitals NHS Foundation Trust, Oxford (L.S.) - all in the United Kingdom; the University of Gothenburg (C.P.) and Sahlgrenska University Hospital (C.H.), Gothenburg, Uppsala University Hospital, Uppsala (M.A., E.L.), Linköping University Hospital, Linköping (P.B., A.-S.B.T.), Umeå University (K.B.) and Norrlands University Hospital (J.E.W.), Umeå, Skåne University Hospital, Malmö (K.K., M.S.), Karolinska Institutet, Solna (A.L., J.N.), and Karolinska University Hospital, Stockholm (L.R.W.) - all in Sweden; the University of Copenhagen (E.W., L.D.J.) and Copenhagen Cleft Palate Center (H.S.A., L.D.J.), Copenhagen, and the Cleft Palate Center, Aarhus (B.K.E., L.L., J.B.N.) - all in Denmark; the University of São Paulo, Bauru, Brazil (M.Z.A., A.P.F., C.G.A.B.G., H.C.M., S.H.A.P.-P., I.E.K.T., R.P.Y.); and Statped (R.A., A.K.H., M.B.K., J.L.) and Statped Sørøst (M.M.), Oslo, and Statped Vest, Bergen (N.-H.P., J.T.) - all in Norway.

PMID: 37646677
PMCID: PMC10880183
DOI: 10.1056/NEJMoa2215162

Randomized Controlled Trial

Timing of Primary Surgery for Cleft Palate

Carrol Gamble et al. N Engl J Med. 2023.

. 2023 Aug 31;389(9):795-807.

doi: 10.1056/NEJMoa2215162.

Authors

Collaborators

TOPS Study Group:
H F Aguiar, L Albery, H S Andersen, M Z Antoneli, M Appelqvist, R Aukner, A Aziz, M Becker, C E Bertier, P Bodling, S Boljanovic, M Bowden, Tvs Brosco, K Brunnegård, M Cadier, G Cairns, J Cajander, S Calladine, L Campbell, L Carney-Venters, J Clayton-Smith, R Cooper, E Conroy, M Devlin, A El-Angbawi, B K Emborg, J Enfält Wikman, P Eyres, H Extence, C Filip, B Fitzpatrick, A P Fukushiro, C Gamble, Cgab Gonçalves, M Hakelius, C Havstam, P Hodgkinson, A K Hvistendahl, L D Jorgensen, J C Jorge, L Kane, K Klinto, M B Kvinnsland, C Larham, J Lemvik, L Leturgie, E Liljerehn, N Lodge, A Lohmander, S McMahon, A Marcusson, H Mark, F Mehendale, N Mercer, H C Miguel, M Moe, T Moitt, J Mooney, M Mulki, K J Munro, E Neovius, J B Nielsen, L Norman, J Nyberg, N-H Pedersen, C Persson, G Phippen, Sha Piazentin-Penna, K Patrick, L Pliskin, L Rigby, P Rorison, G Semb, R Slator, L Southby, M Sporre, W Shaw, A Smyth, M C Swan, A-Sb Taleman, J Tangstad, P Tate, Iek Trindade, Iek Underwood, S van Eeden, H Vindenes, T Walsh, D Weichart, L R Westberg, D Whitby, E Willadsen, P R Williamson, R P Yamashita

Affiliation

¹ From the University of Liverpool (C.G., R.C., E.C., L.P., P.R.W.) and Alder Hey Children's NHS Foundation Trust (S.M.), Liverpool, Royal Hospital for Sick Children (G.C., N.L.) and the University of Edinburgh (F.M.), Edinburgh, Northern and Yorkshire Regional Cleft Lip and Palate Service (S.C.) and Leeds General Infirmary (C.L.), Leeds, Cleft Care Scotland, Glasgow (L.C.), Bristol Dental Hospital, Bristol (L.A.), the University of Manchester (J.C.-S., A.E.-A., G.S., K.M., T.W., W.S.) and Manchester University NHS Foundation Trust (M.B., K.P.), Manchester, Birmingham Children's Hospital (B.F.) and Birmingham Women's and Children's NHS Foundation Trust (I.U.), Birmingham, Salisbury District Hospital, Salisbury (G.P.), Royal Victoria Infirmary, Newcastle upon Tyne (L.R., S.E.), and Oxford University Hospitals NHS Foundation Trust, Oxford (L.S.) - all in the United Kingdom; the University of Gothenburg (C.P.) and Sahlgrenska University Hospital (C.H.), Gothenburg, Uppsala University Hospital, Uppsala (M.A., E.L.), Linköping University Hospital, Linköping (P.B., A.-S.B.T.), Umeå University (K.B.) and Norrlands University Hospital (J.E.W.), Umeå, Skåne University Hospital, Malmö (K.K., M.S.), Karolinska Institutet, Solna (A.L., J.N.), and Karolinska University Hospital, Stockholm (L.R.W.) - all in Sweden; the University of Copenhagen (E.W., L.D.J.) and Copenhagen Cleft Palate Center (H.S.A., L.D.J.), Copenhagen, and the Cleft Palate Center, Aarhus (B.K.E., L.L., J.B.N.) - all in Denmark; the University of São Paulo, Bauru, Brazil (M.Z.A., A.P.F., C.G.A.B.G., H.C.M., S.H.A.P.-P., I.E.K.T., R.P.Y.); and Statped (R.A., A.K.H., M.B.K., J.L.) and Statped Sørøst (M.M.), Oslo, and Statped Vest, Bergen (N.-H.P., J.T.) - all in Norway.

PMID: 37646677
PMCID: PMC10880183
DOI: 10.1056/NEJMoa2215162

Abstract

Background: Among infants with isolated cleft palate, whether primary surgery at 6 months of age is more beneficial than surgery at 12 months of age with respect to speech outcomes, hearing outcomes, dentofacial development, and safety is unknown.

Methods: We randomly assigned infants with nonsyndromic isolated cleft palate, in a 1:1 ratio, to undergo standardized primary surgery at 6 months of age (6-month group) or at 12 months of age (12-month group) for closure of the cleft. Standardized assessments of quality-checked video and audio recordings at 1, 3, and 5 years of age were performed independently by speech and language therapists who were unaware of the trial-group assignments. The primary outcome was velopharyngeal insufficiency at 5 years of age, defined as a velopharyngeal composite summary score of at least 4 (scores range from 0 to 6, with higher scores indicating greater severity). Secondary outcomes included speech development, postoperative complications, hearing sensitivity, dentofacial development, and growth.

Results: We randomly assigned 558 infants at 23 centers across Europe and South America to undergo surgery at 6 months of age (281 infants) or at 12 months of age (277 infants). Speech recordings from 235 infants (83.6%) in the 6-month group and 226 (81.6%) in the 12-month group were analyzable. Insufficient velopharyngeal function at 5 years of age was observed in 21 of 235 infants (8.9%) in the 6-month group as compared with 34 of 226 (15.0%) in the 12-month group (risk ratio, 0.59; 95% confidence interval, 0.36 to 0.99; P = 0.04). Postoperative complications were infrequent and similar in the 6-month and 12-month groups. Four serious adverse events were reported (three in the 6-month group and one in the 12-month group) and had resolved at follow-up.

Conclusions: Medically fit infants who underwent primary surgery for isolated cleft palate in adequately resourced settings at 6 months of age were less likely to have velopharyngeal insufficiency at the age of 5 years than those who had surgery at 12 months of age. (Funded by the National Institute of Dental and Craniofacial Research; TOPS ClinicalTrials.gov number, NCT00993551.).

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Comment in

Timing of Primary Surgery for Cleft Palate.
Denadai R, Lo LJ. Denadai R, et al. N Engl J Med. 2023 Dec 7;389(23):2208-2209. doi: 10.1056/NEJMc2311517. N Engl J Med. 2023. PMID: 38063333 No abstract available.
Timing of Primary Surgery for Cleft Palate. Reply.
Gamble C, Munro K. Gamble C, et al. N Engl J Med. 2023 Dec 7;389(23):2209. doi: 10.1056/NEJMc2311517. N Engl J Med. 2023. PMID: 38063334 No abstract available.

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References

1. Burg ML, Chai Y, Yao CA, Magee W III, Figueiredo JC. Epidemiology, etiology, and treatment of isolated cleft palate. Front Physiol 2016;7:67. - PMC - PubMed
1. Yow M, Jin A, Yeo GSH. Epidemiologic trends of infants with orofacial clefts in a multiethnic country: a retrospective population-based study. Sci Rep 2021;11: 7556. - PMC - PubMed
1. IPDTOC Working Group. Prevalence at birth of cleft lip with or without cleft palate: data from the International Perinatal Database of Typical Oral Clefts (IPDTOC). Cleft Palate Craniofac J 2011;48:66–81. - PubMed
1. Sandy J, Davies A, Humphries K, Ireland T, Wren Y. Cleft lip and palate: care configuration, national registration, and research strategies. J World Fed Orthod 2020;9:Suppl 3:S40–S44. - PMC - PubMed
1. Peterson-Falzone SJ. Optimal age for palatoplasty to facilitate normal speech development: what is the evidence? In: Berkowitz S, ed. Cleft lip and palate. Berlin: Springer, 2013: 787–802 (10.1007/3-540-30020-1_45). - DOI

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[1] Burg ML, Chai Y, Yao CA, Magee W III, Figueiredo JC. Epidemiology, etiology, and treatment of isolated cleft palate. Front Physiol 2016;7:67. - PMC - PubMed

[2] Burg ML, Chai Y, Yao CA, Magee W III, Figueiredo JC. Epidemiology, etiology, and treatment of isolated cleft palate. Front Physiol 2016;7:67. - PMC - PubMed

[3] Yow M, Jin A, Yeo GSH. Epidemiologic trends of infants with orofacial clefts in a multiethnic country: a retrospective population-based study. Sci Rep 2021;11: 7556. - PMC - PubMed

[4] Yow M, Jin A, Yeo GSH. Epidemiologic trends of infants with orofacial clefts in a multiethnic country: a retrospective population-based study. Sci Rep 2021;11: 7556. - PMC - PubMed

[5] IPDTOC Working Group. Prevalence at birth of cleft lip with or without cleft palate: data from the International Perinatal Database of Typical Oral Clefts (IPDTOC). Cleft Palate Craniofac J 2011;48:66–81. - PubMed

[6] IPDTOC Working Group. Prevalence at birth of cleft lip with or without cleft palate: data from the International Perinatal Database of Typical Oral Clefts (IPDTOC). Cleft Palate Craniofac J 2011;48:66–81. - PubMed

[7] Sandy J, Davies A, Humphries K, Ireland T, Wren Y. Cleft lip and palate: care configuration, national registration, and research strategies. J World Fed Orthod 2020;9:Suppl 3:S40–S44. - PMC - PubMed

[8] Sandy J, Davies A, Humphries K, Ireland T, Wren Y. Cleft lip and palate: care configuration, national registration, and research strategies. J World Fed Orthod 2020;9:Suppl 3:S40–S44. - PMC - PubMed

[9] Peterson-Falzone SJ. Optimal age for palatoplasty to facilitate normal speech development: what is the evidence? In: Berkowitz S, ed. Cleft lip and palate. Berlin: Springer, 2013: 787–802 (10.1007/3-540-30020-1_45). - DOI

[10] Peterson-Falzone SJ. Optimal age for palatoplasty to facilitate normal speech development: what is the evidence? In: Berkowitz S, ed. Cleft lip and palate. Berlin: Springer, 2013: 787–802 (10.1007/3-540-30020-1_45). - DOI

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Timing of Primary Surgery for Cleft Palate

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