Objective To investigate the association between the sidedness of orofacial clefts and additional congenital malformations.

Design Linkage of a national registry of cleft births to national administrative data of hospital admissions

Setting National Health Service, England

Participants 2,007 children born with cleft lip +-alveolus (CL+-A) and 2,724 with cleft lip and palate (CLP) born between 2000 and 2012.

Main outcome measure The proportion of children with ICD-10 codes for additional congenital malformations by the sidedness (left, right or bilateral) of orofacial clefts.

Results For CL+-A phenotypes, there was no evidence for a difference in the prevalence of additional anomalies between left (22%, reference), right (22%, aOR 1.02, 95% CI 0.80 to 1.28; p= 0.90) and bilateral clefts (23%, aOR 1.09, 95% CI 0.75 to 1.57; p= 0.66). For CLP phenotypes, there was evidence of a lower prevalence of additional malformations in left (23%, reference) compared to right (32%, aOR 1.54, 95% CI 1.25 to 1.91; p <0.001) and bilateral clefts (33%, aOR 1.64, 95% CI 1.35 to 1.99; p<0.001).

Conclusions The prevalence of additional congenital malformations was similar across sidedness subtypes with CL+-A phenotypes but was different for sidedness subtypes within CLP cases. These data support the hypothesis that CL+-A has a different underlying aetiology from CLP and that within the CLP phenotype, right sided CLP may lie closer in aetiology to bilateral CLP than it does to left sided CLP.

The authors have declared no competing interest.

Professor Sarah Lewis is supported by a project grant from the Medical Research Council (MR/T002093/1)

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

2 national data sets in the UK: CRANE (Cleft Registry and Audit Network) and HES (Hospital Episode Statistics for all hospital admissions in NHS England). This study is exempt from NHS Research Authority ethics approval as it involves the analysis of an existing anonymised dataset that is collected for the purpose of service evaluation.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

↵ϕ Joint First Authors

Conflict of Interest Statement: The authors declare that there is no conflict of interest

Financial support: SL is supported by a project grant from the Medical Research Council (MR/T002093/1)

All data produced in the present work are contained in the manuscript