Abstract
Objective
To assess the range and frequency of additional congenital malformations identified among children born alive with CL/P.
Design
Analysis of patient-level data from a national registry of cleft births linked to national administrative data of hospital admissions.
Setting
National Health Service, England.
Patients
Children born between 2000 and 2012 receiving cleft care in English NHS hospitals.
Outcome Measures
The proportion of children with ICD-10 codes for additional congenital malformations, according to cleft type.
Results
The study included 9403 children. Of these 2114 (22.5%) had CL±A, 4509 (48.0%) had CP, 1896 (20.2%) had UCLP, and 884 (9.4%) had BCLP. A total of 3653 (38.8%) children had additional congenital malformations documented in their hospital admission records. The prevalence of additional congenital malformations was greatest among children with CP (53.0%), followed by those with BCLP (33.5%), UCLP (26.3%), and then CL±A (22.2%) (P < .001). Among those with UCLP, children with right-sided clefts were more likely to have additional malformations than those with left-sided clefts (31.6% vs 23.0%, P < .001). Malformations of the skeletal system and circulatory system were most common, affecting 10.5% and 10.2% of the included children, respectively. A total of 16.8% of children had additional congenital malformations affecting 2 or more structural systems.
Conclusions
Congenital malformations are common among children born alive with a cleft, affecting over half of some cleft subgroups. Given the frequency of certain structural malformations, clinicians should consider standardized screening for these children. Establishing good links with pediatric and genetic services is recommended.
Introduction
Orofacial clefts (OFCs) are among the most common major congenital malformations in humans, occurring in an estimated 1 in 700 live births worldwide. 1 OFCs may affect only the lip ± alveolus (CL±A), only the palate (CP), or both (CLP). Clefts affecting the lip can be further categorized as unilateral (UCL and UCLP) or bilateral (BCL and BCLP). Broadly, OFCs result from errors during the normal processes of craniofacial development that occur between 5 and 12 weeks of embryonic life. The embryological and genetic basis of CL±A, CLP, and CP are understood to be distinct, which will have implications for the distribution of the associated conditions.2,3
Although an OFC can occur in isolation, they may also occur alongside other congenital malformations. The reported frequency of these additional malformations varies between studies, ranging from 2.9% to 36.7%.4–17 In some cases, the pattern of malformations present may constitute a recognizable association or “syndrome,” and so give insight into the underlying etiology of the cleft. Recognizing the risk of additional malformations among babies presenting with an OFC is important for optimal medical management of the child, supporting accurate reproductive counseling for parents, prognostic and therapeutic evaluations, and informing etiologic research.
In England, the prevalence of additional congenital malformations occurring among children born alive with a cleft is currently unknown, and routine screening for additional malformations is not currently performed for children presenting with a cleft. Our group has previously reported cleft-related care and outcomes separately for those considered to have an isolated cleft and those with syndromes or associated anomalies.18–20 However, the list of diagnoses used to identify the latter group depends on the purpose of the study and outcomes of interest. The full range or frequency of structural malformations has not been explored in this population.
Using the national cleft registry linked to a national database of all National Health Service (NHS) hospital admissions in England, we sought to quantify the prevalence of additional congenital malformations occurring together with an OFC and to describe the range of these malformations, exploring whether differences exist between the main cleft type subgroups.
Methods
Data Source
The study cohort was identified in the Cleft Registry and Audit NEtwork (CRANE) database (www.crane-database.org.uk). CRANE collects information on all live-born children with a CL/P in England, Wales, and Northern Ireland. There is no time limit on when the cleft must be diagnosed in order to be included in the registry, though typically identification occurs antenatally or at/soon after birth, which was the case for 84.2% of those with diagnosis time reported. Children whose parents had given consent for their child's records to be included in CRANE (verified consent rate ∼98%) were eligible to be linked to the Hospital Episode Statistics (HES) database. The HES database (www.digital.nhs.uk) contains records on all diagnoses and treatments made and given during admissions to NHS hospitals in England. The linked dataset contained records on births up to December 31, 2012, and hospital admissions up to March 31, 2015. 21 The NHS is a state-funded healthcare system that provides organized multidisciplinary care for all children born with a cleft in England.
HES data are collected by professional health coders based in each NHS provider in England primarily for the purpose of reimbursement. Records from each hospital episode are reviewed by coders and the International Classification of Diseases—Tenth Revision (ICD-10) is used to capture diagnoses. Full information on the HES data processing cycle and quality is publically available. 22
Patients
A total of 10 483 children who were born alive between January 1, 2000, and December 31, 2012, and registered in CRANE were successfully linked to HES records. Of these, 1080 were excluded because either cleft type information was missing (n = 239) or there was no agreement on cleft type between the 2 data sources (n = 841). In total, 9403 children were included in the analyses.
Cleft Type
Clefts were grouped as cleft lip ± alveolus involvement (CL±A), cleft palate only (CP), unilateral cleft lip and palate (UCLP), or bilateral cleft lip and palate (BCLP) according to data held on the CRANE database and the diagnosis codes using the ICD-10 system in any of the available HES records.
Diagnoses of Additional Congenital Malformations
ICD-10 codes were used to identify congenital malformations in the study cohort. HES records for any single admission contain at least 14 diagnosis code fields. The ICD-10 diagnostic codes representing congenital malformations and chromosomal abnormalities (Q00-Q99; see Appendix 1), in any diagnosis field of a HES record, were used to identify a child as having a congenital malformation in addition to their cleft. These malformations were categorized according to the body or organ system they affected.
Analyses
The proportion of children with ICD-10 codes for congenital malformations (listed in Appendix 1) was examined. These rates were determined for the 4 cleft type subgroups and separately for right- and left-sided unilateral clefts. Since the cleft type distribution varies between males and females, the rates were also reported according to sex. The ethnic background of children included in the study was obtained from HES, and the corresponding rates for additional congenital malformations were calculated.
The number of different body or organ systems with malformations was summed for each child and also reported by cleft type. “Chromosomal abnormalities not elsewhere specified” (Q90-Q99) were not included in these particular analyses, as the aim was to sum the specific body systems affected by physical malformations, rather than the underlying cause. Although certain chromosomal diagnoses may be associated with a high likelihood of particular malformations, these were not assumed to be present unless otherwise recorded.
The χ2 test was used to assess variations in proportions across nonordered groups, such as cleft type classification. A P value <.05 was considered statistically significant. All statistical calculations were performed in Stata V.15 (Statacorp).
Ethical Considerations
The study is exempt from NHS Health Research Authority ethics approval as it involves the analysis of an existing anonymized dataset that is collected for the purpose of service evaluation. 23
Results
Patient Characteristics
Table 1 shows the characteristics of the 9403 children included in the analyses. 2114 (22.5%) had CL±A, 4509 (48.0%) had CP, 1896 (20.2%) had UCLP, and 884 (9.4%) had BCLP. Among those with a unilateral cleft affecting the lip, left-sided clefts were more common, presenting in 1227 (64.5%) out of 1904 with CL±A, and in 1179 (62.7%) out of 1881 children with UCLP who had cleft laterality reported. There were more males than females, which is typical for a cleft population, 24 and the majority of children were classified as being of white ethnicity, which is consistent with the English general population.
Characteristics of the Children Included in the Analyses and the Number and Percentage of Those With Additional Malformations, According to Those Characteristics.
Prevalence of Additional Malformations
Overall, 3653 (38.8%) children had diagnoses of additional congenital malformations in their HES records. These rates varied significantly according to cleft type and were highest among those with CP (53.0%), followed by those with BCLP (33.5%), UCLP (26.3%), and then CL±A (22.2%) (P < .001).
Rates of additional malformations were associated with laterality of the cleft among children with UCLP but not CL±A (Table 2). Compared to left-sided UCLPs, additional malformations were more prevalent among right-sided UCLPs (23.0% vs 31.6%, P < .001). Sex was also found to be associated with risk of additional malformations among those with CP (50.4% among girls and 56.0% among boys, P < .001) (Table 3) but not among those with other cleft types. The prevalence of additional malformations was found to vary according to ethnic group. Among those from a white background, 38.6% had additional malformations. Although the corresponding rates were higher among those from Mixed and Asian backgrounds (53.4% and 47.0%, respectively), these differences should be interpreted with caution due to low representation from minority ethnic groups and a relatively high proportion of missing data.
Number and Percentage of Children Born With a Cleft Who Have Additional Congenital Malformations, According to Laterality of the Cleft Lip.a
P value for difference in proportion of children with additional congenital malformations between left- and right-sided unilateral cleft lip. Note, 192/2114 children with CL±A had bilateral cleft lip. 18/2114 children with CL±A and 15/1896 children with UCLP were missing laterality information.
Number and Percentage of Children Born With a Cleft Who Have Additional Congenital Malformations, According to Sex and Cleft Type.a
P value for difference in proportion of children with additional congenital malformations between the sexes.
Body Systems Affected by Additional Malformations
Table 4 shows the prevalence of malformations affecting each body system, as identified by different ICD-10 codes. Over 10% of the study cohort had at least one malformation of the circulatory system. The predominant malformations were those affecting the cardiac septa and those of the great arteries (identified in 7.6% and 5.2% of the cohort, respectively—see Appendix 1 for a further breakdown of ICD-10 codes and the number of children with these diagnoses). Musculoskeletal malformations were also identified in over 10% of the cohort. Deformities of the feet were most prevalent, affecting 3.5% of children, followed by malformations of the skull and face bones, which were identified in 2.8% of children. Although 8.3% of the cohort were identified as having malformations of the digestive system, these were primarily attributed to malformations of the tongue, mouth, and pharynx (6.1% of children).
Number and Percentage of Children Born With a Cleft Who Have Additional Congenital Malformations, According to the Type of Malformation and Cleft Type.a
Abbreviation: ICD-10, International Classification of Diseases—Tenth Edition.
P value for difference in proportion of children with additional congenital malformations between cleft types.
The most common system affected by malformations varied according to cleft type. Among those with CL±A and BCLP, malformations and deformations of the musculoskeletal system were most common, affecting 6.0% and 11.2% of the subgroups, respectively. Among those with UCLP, malformations of the circulatory system were most common, affecting 7.3%. Although malformations affecting these 2 systems were even more prevalent among children with CP (>14%), “other congenital malformations” were identified in 1482 out of 4509 children (32.9%) with CP; 1338 (29.7% of those with CP) of these had ICD-10 code Q87 “Other specified congenital malformation syndromes affecting multiple systems.” A further breakdown of this code revealed that 1230 (27.3%) had “Congenital malformation syndromes predominantly affecting facial appearance” (ICD-10 Q87.0). This diagnosis was much less common among those with CL±A (0.7%), UCLP (0.9%), and BCLP (1.5%). The only body system whereby the rate of additional malformations did not vary according to cleft type was the respiratory system. These malformations were present in approximately 5% of each cleft type subgroup.
Number of Systems Affected by Additional Malformations
Table 5 shows the number and percentage of children who had multiple (≥2) body systems (eg, nervous, eye/ear/face/neck, circulatory, respiratory, digestive, genital/reproductive, urinary, and musculoskeletal systems) affected by additional malformations. Overall, 16.7% of the study cohort had malformations across multiple body systems, in addition to the cleft lip and/or palate. This rate varied considerably between cleft types and was highest among those with CP (38.5%) and lowest among those with CL±A (5.1%) (P < .001).
Number of Body Systems Affected by Additional Congenital Malformations, According to Cleft Type.
Discussion
Key Findings
The current study describes the frequency and range of additional congenital malformations in a cohort of children born alive with a cleft in England, based on routinely collected administrative hospital data. It found that congenital malformations occurring in addition to an OFC are common and vary by cleft type, affecting approximately 1 in every 2 children with CP, 1 in every 3 with BCLP, 1 in every 4 with UCLP, and 1 in every 4.5 with CL±A.
Malformations affecting 2 or more body systems, in addition to the cleft, were also common among those with CP, affecting 38.5% of the entire subgroup. Congenital malformations affecting multiple systems were less common among the other cleft subgroups but they were not rare. Malformations of the musculoskeletal system and circulatory system were frequently occurring. Among children with CP, over one quarter had diagnosis codes representing malformation syndromes predominantly affecting facial appearance. This category would include, for example, diagnoses such as acrocephalosyndactyly syndromes, Goldenhar syndrome, orofacial-digital syndromes, and Pierre Robin sequence.
Comparisons With Other Studies
The present study found 38.8% of all children born alive with a cleft had at least one additional malformation. To our knowledge, this is the highest rate reported in the last 30 years, even when compared with studies based on data from congenital anomaly registers that include pregnancies that were terminated and stillbirths.5–7,9,16 These studies have reported overall rates of additional malformations affecting between 21.0% and 36.7% of babies with an OFC. Of the previous studies including only live births, only 2 reported that additional malformations occurred in more than 30% of children with a cleft. Beriaghi et al 10 found that out of 1127 children born between 1980 and 2000 with a cleft in the United States, 32.2% had additional malformations. Similarly, Pereira et al 15 reported that out of 701 children born with a cleft and treated in a tertiary cleft center in Southern Portugal between 1981 and 2012, 31.2% had additional malformations.
Previous studies using CRANE-HES linked English data that report cleft-related care or outcomes have, on average, identified approximately 22% of all children with a cleft as having additional anomalies or syndromes.18–20 In those previous studies, the list of congenital malformations and chromosomal abnormalities used to identify these children was primarily restricted to those of the nervous system, circulatory system, and some syndromes frequently occurring among children with a cleft that were thought to influence the care or outcomes being reported. The current study has expanded this definition to determine the range and frequency of all congenital malformations occurring among the cleft population, which accounts for the difference in reported rates. This highlights that reported rates of additional malformations or syndromes will depend on the definition used and the purpose for which the malformations were detected.
In the present study, the prevalence of additional malformations was not evenly distributed across the cleft type subgroups. Children with CP had the highest rate of additional malformations, while those with CL±A had the lowest rate. These relative differences are consistent with other European studies comparing the prevalence of congenital malformations between cleft types.5,15,16 Our finding that 53.0% of children with CP had an additional malformation is higher than the previously reported highest rate of 46.7% by Stoll et al, 5 which, contrary to this study, included pregnancies that were terminated and stillbirths. Our finding that 22.2% of children with CL±A had additional malformations is similar to rates reported by others, including those using congenital anomaly registers and others reporting rates for live births only.15,17
A valuable aspect of our study is reporting additional congenital anomaly rates separately for those with UCLP and BCLP. The majority of previous studies have reported rates for these children combined. This study provides evidence that children with BCLP are more likely to have additional malformations than those with UCLP, which is consistent with the findings of the few small studies that have reported rates separately in the past.4,12,25
A novel finding from the present study is that right-sided UCLPs carry a significantly higher chance of additional malformations compared with left-sided UCLPs. The laterality of cleft phenotypes should therefore be taken into account when counseling parents and when considering additional screening.
In agreement with our study, malformations of the musculoskeletal and circulatory systems are often the most frequently cited in the literature, particularly for children with a cleft affecting the palate.4,10,15 However, there are varying reports regarding the exact prevalence of these additional malformations and their specific nature, which are likely influenced by methodological factors. As the present study included over 9000 children identified in a national cleft registry linked to national hospital admission records, it is felt that the rates of additional malformations affecting each body system reported here are reliable for children born alive with a cleft in England.
Comparison with studies reporting the prevalence and range of additional malformations among children with a cleft is challenging due to the different methods employed to identify malformations and the different inclusion criteria used. For example, differences between studies may relate to what constitutes a congenital malformation and to the source of information. Also, the length of time that children are followed up for is another factor to consider and whether the study also includes termination of pregnancies and stillbirths or only children born alive. Several studies are based on patients attending just one cleft clinic, which may not be representative of the wider cleft population, and the location of the study may be important, given the possibility of varying rates of additional malformations across different ethnic groups, as indicated in the current study.
Implications
The distinction between true isolated OFC and OFC with additional malformations has important implications for reproductive counseling of affected families. Most cases of isolated OFC are understood to have a multifactorial cause, likely arising from a complex interaction between inherited susceptibility and environmental risk factors. 26 In such cases, the likelihood of identifying a single, causative genetic variation even by exhaustive genetic investigation is relatively low, 27 and so counseling of families is typically based on empirical recurrence risk figures from large population studies. In the absence of strong family history, these figures generally quote a risk that is elevated compared to the general population, but still relatively low in absolute terms. 28
By contrast, the yield from genetic investigations in cases where OFC is accompanied by additional structural malformations is incrementally increased. 29 A specific genetic diagnosis can enable tailoring of medical care, since many examples have specific additional implications for health and/or development. This can also allow more specific prognostic information to be offered to families. Furthermore, some genetic diagnoses may be associated with a substantially elevated risk of recurrence in a future pregnancy, and so their recognition can enable the provision of reproductive options such as preimplantation genetic diagnosis to couples at risk. With the increasing availability of powerful genomic technologies for the investigation of pediatric developmental disorders in the UK, 30 early recognition of OFC with associated malformations is crucial to identify those patients within cleft cohorts who are most likely to benefit from a genetic assessment and investigation.
The relatively high frequency of particular additional congenital malformations identified in this study, including those affecting the circulatory system, raises the question as to whether systematic screening for malformations should be integrated into standard care for children with OFC. Where prenatal malformation screening with ultrasonography is available, we believe that sonographers need to have a detailed understanding of the nature and frequency of associated malformations to allow directed systematic scanning where an OFC is identified. Furthermore, we believe that recognizing and understanding the implications of the associated malformations most frequently occurring among children with a cleft and the different cleft phenotypes is essential when counseling parents after diagnosis. This information is important for the delivery of support and care to the family and also useful in the design of cleft care resources.
Strengths and Limitations
This is a national population-based study reporting additional congenital malformations in over 9000 children born alive with OFCs during a relatively recent 13-year birth period. The study has an important strength: it is based on a national cleft registry database that aims to include all children born alive with a cleft in England from 2000 onward. Records from the registry were linked to national administrative hospital data, which includes records of all children treated for a cleft in English National Health Service hospitals. HES captures a vast range of information on each patient, including ICD-10 diagnosis codes. As the NHS is a publicly funded national healthcare system, providing care to at least 95% of the population, our sample is unlikely to be confounded by ascertainment bias based on socioeconomic status, and hence can be assumed to be representative of the population studied.
Another strength is our ability to report malformation rates according to 4 main cleft subgroups and to further examine the laterality of cleft lip involvement, as well as sex. The findings are not only important when counseling parents or when considering referral for screening but they also have potential implications for future research investigating the causality of cleft affecting the lip and palate, be it genetic or environmental.
This study was restricted to children born alive. Spontaneous abortions, elective terminations, and stillborn fetuses were not possible to include. Furthermore, as there is no standard protocol for evaluating other body systems for anomalies in children presenting with a cleft in England, there may well be subclinical and untreated anomalies that have been missed in the study population. The true prevalence of additional malformations is, therefore, likely to be underrepresented. From a clinical perspective, true prevalence would be ideal for antenatal counseling purposes. However, for future planning of health care services, the rates of additional malformations in live-born children are most relevant.
Although the use of ICD-10 codes allowed us to report many congenital malformations, HES restricts the entry of these codes to 4 characters (eg, Q87.0). This meant that some codes were not sensitive enough to distinguish between certain diagnoses (eg, Pierre Robin sequence and Goldenhar syndrome share the same 4 character ICD-10 code). Furthermore, ICD-10 codes utilized in HES tend to focus on a physical diagnosis or phenotype, rather than the underlying genetic cause. This means the prevalence of specific genetic and/or syndromic diagnoses associated with orofacial clefts and other congenital malformations could not be reported.
Finally, subgroup analyses showing the proportion of children with additional malformations according to ethnic background were limited by missing data and relatively low representation by minority ethnic groups. Differences in the prevalence of additional malformations among those with OFCs from different ethnic backgrounds would benefit from further research.
Summary
Identifying the frequency and range of additional structural malformations occurring among children born with a cleft is important for counseling parents and for planning and commissioning cleft services. Implementing routine screening for certain cleft phenotypes is recommended based on the high prevalence of additional malformations identified in this study. Good links with local genetic and pediatric services (particularly cardiovascular, musculoskeletal, urogenital, gastrointestinal, and respiratory) are also recommended as associated malformations of these nature occur individually in over 5% of live cleft presentations in England. Priorities for future work include investigating the etiological links between OFCs and additional malformations, exploring additional malformations according to ethnicity and the laterality of the cleft, establishing the prevalence of other diagnoses, such as neurodevelopmental disorders, and investigating potential delays in the identification of additional structural anomalies. These data would help to inform both a rational approach to screening and planning of care for children affected by congenital malformations.
Footnotes
Acknowledgments
The authors thank NHS Digital for providing and permitting reuse of Hospital Episode Statistics data used in this study. The authors also thank Mr David Chong, Plastic Surgeon at The Royal Children's Hospital Melbourne, for his insight and suggestion to examine laterality of cleft lip involvement.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was carried out by the CRANE Database team, whose work is funded by the National Specialised Commissioning Group for England, the Wales Specialised Health Services Committee, and the Northern Ireland Specialist Services Commissioning Team.
Diagnostic Codes Used to Identify Congenital Malformations, and the Number (%) of Children in the Cleft Cohort With These Codes in Their Hospital Episode Statistics History.
| ICD-10 code | Description | N = 9403 | |
|---|---|---|---|
| n | (%) | ||
| Congenital malformations of the nervous system | 335 | (3.6) | |
| Q00 | Anencephaly and similar malformations | 2 | (0.0) |
| Q01 | Encephalocele | 5 | (0.1) |
| Q02 | Microcephaly | 142 | (1.5) |
| Q03 | Congenital hydrocephalus | 54 | (0.6) |
| Q04 | Other congenital malformations of brain | 152 | (1.6) |
| Q05 | Spina bifida | 15 | (0.2) |
| Q06 | Other congenital malformations of spinal cord | 17 | (0.2) |
| Q07 | Other congenital malformations of nervous system | 30 | (0.3) |
| Congenital malformations of eye, ear, face and neck | 514 | (5.5) | |
| Q10 | Congenital ptosis | 96 | (1.0) |
| Q11 | Anophthalmos, microphthalmos and macrophthalmos | 44 | (0.5) |
| Q12 | Congenital lens malformations | 30 | (0.3) |
| Q13 | Congenital malformations of anterior segment of eye | 71 | (0.8) |
| Q14 | Congenital malformations of posterior segment of eye | 71 | (0.8) |
| Q15 | Other congenital malformations of eye | 29 | (0.3) |
| Q16 | Congenital malformations of ear causing impairment of hearing | 43 | (0.5) |
| Q17 | Other congenital malformations of ear | 161 | (1.7) |
| Q18 | Other congenital malformations of face and neck | 156 | (1.7) |
| Congenital malformations of the circulatory system | 956 | (10.2) | |
| Q20 | Congenital malformations of cardiac chambers and connections | 67 | (0.7) |
| Q21 | Congenital malformations of cardiac septa | 714 | (7.6) |
| Q22 | Congenital malformations of pulmonary and tricuspid valves | 93 | (1.0) |
| Q23 | Congenital malformations of aortic and mitral valves | 78 | (0.8) |
| Q24 | Other congenital malformations of heart | 143 | (1.5) |
| Q25 | Congenital malformations of great arteries | 491 | (5.2) |
| Q26 | Congenital malformations of great veins | 35 | (0.4) |
| Q27 | Other congenital malformations of peripheral vascular system | 33 | (0.4) |
| Q28 | Other congenital malformations of circulatory system | 5 | (0.1) |
| Congenital malformations of the respiratory system | 487 | (5.2) | |
| Q30 | Congenital malformations of nose | 239 | (2.5) |
| Q31 | Congenital malformations of larynx | 182 | (1.9) |
| Q32 | Congenital malformations of trachea and bronchus | 87 | (0.9) |
| Q33 | Congenital malformations of lung | 33 | (0.4) |
| Q34 | Other congenital malformations of respiratory system | 22 | (0.2) |
| Other congenital malformations of the digestive system | 776 | (8.3) | |
| Q38 | Other congenital malformations of tongue, mouth and pharynx | 575 | (6.1) |
| Q39 | Congenital malformations of oesophagus | 48 | (0.5) |
| Q40 | Other congenital malformations of upper alimentary tract | 40 | (0.4) |
| Q41 | Congenital absence, atresia and stenosis of small intestine | 20 | (0.2) |
| Q42 | Congenital absence, atresia and stenosis of large intestine | 27 | (0.3) |
| Q43 | Other congenital malformations of intestine | 102 | (1.1) |
| Q44 | Congenital malformations of gallbladder, bile ducts and liver | 10 | (0.1) |
| Q45 | Other congenital malformations of digestive system | 1 | (0.0) |
| Congenital malformations of the genital organs | 480 | (5.1) | |
| Q50 | Congenital malformations of ovaries, fallopian tubes and broad ligaments | 0 | (0.0) |
| Q51 | Congenital malformations of uterus and cervix | 4 | (0.0) |
| Q52 | Other congenital malformations of female genitalia | 20 | (0.2) |
| Q53 | Undescended testicle | 289 | (3.1) |
| Q54 | Hypospadias | 126 | (1.3) |
| Q55 | Other congenital malformations of male genital organs | 120 | (1.3) |
| Q56 | Indeterminate sex and pseudohermaphroditism | 14 | (0.1) |
| Congenital malformations of the urinary system | 225 | (2.4) | |
| Q60 | Renal agenesis and other reduction defects of kidney | 37 | (0.4) |
| Q61 | Cystic kidney disease | 42 | (0.4) |
| Q62 | Congenital obstructive defects of renal pelvis and congenital malformations of ureter | 100 | (1.1) |
| Q63 | Other congenital malformations of kidney | 81 | (0.9) |
| Q64 | Other congenital malformations of urinary system | 18 | (0.2) |
| Congenital malformations and deformations of the musculoskeletal system | 990 | (10.5) | |
| Q65 | Congenital deformities of hip | 86 | (0.9) |
| Q66 | Congenital deformities of feet | 330 | (3.5) |
| Q67 | Congenital musculoskeletal deformities of head, face, spine and chest | 164 | (1.7) |
| Q68 | Other congenital musculoskeletal deformities | 100 | (1.1) |
| Q69 | Polydactyly | 65 | (0.7) |
| Q70 | Syndactyly | 84 | (0.9) |
| Q71 | Reduction defects of upper limb | 54 | (0.6) |
| Q72 | Reduction defects of lower limb | 34 | (0.4) |
| Q73 | Reduction defects of unspecified limb | 6 | (0.1) |
| Q74 | Other congenital malformations of limb(s) | 113 | (1.2) |
| Q75 | Other congenital malformations of skull and face bones | 267 | (2.8) |
| Q76 | Congenital malformations of spine and bony thorax | 106 | (1.1) |
| Q77 | Osteochondrodysplasia with defects of growth of tubular bones and spine | 27 | (0.3) |
| Q78 | Other osteochondrodysplasias | 43 | (0.5) |
| Q79 | Congenital malformations of the musculoskeletal system, not elsewhere classified | 67 | (0.7) |
| Other congenital malformations | 1691 | (18.0) | |
| Q80 | Congenital ichthyosis | 1 | (0.0) |
| Q81 | Epidermolysis bullosa | 1 | (0.0) |
| Q82 | Other congenital malformations of skin | 180 | (1.9) |
| Q83 | Congenital malformations of breast | 7 | (0.1) |
| Q84 | Other congenital malformations of integument | 20 | (0.2) |
| Q85 | Phakomatoses, not elsewhere classified | 10 | (0.1) |
| Q86 | Congenital malformation syndromes due to known exogenous causes, not elsewhere classified | 80 | (0.9) |
| Q87 | Other specified congenital malformation syndromes affecting multiple systems | 1438 | (15.3) |
| Q89 | Other congenital malformations, not elsewhere classified | 117 | (1.2) |
| Chromosomal abnormalities, not elsewhere classified | 384 | (4.1) | |
| Q90 | Down syndrome | 42 | (0.4) |
| Q91 | Edwards syndrome and Patau syndrome | 32 | (0.3) |
| Q92 | Other trisomies and partial trisomies of the autosomes, not elsewhere classified | 59 | (0.6) |
| Q93 | Monosomies and deletions from the autosomes, not elsewhere classified | 177 | (1.9) |
| Q95 | Balanced rearrangements and structural markers, not elsewhere classified | 23 | (0.2) |
| Q96 | Turner syndrome | 15 | (0.2) |
| Q97 | Other sex chromosome abnormalities, female phenotype, not elsewhere classified | 6 | (0.1) |
| Q98 | Other sex chromosome abnormalities, male phenotype, not elsewhere classified | 26 | (0.3) |
| Q99 | Other chromosome abnormalities, not elsewhere classified | 150 | (1.6) |
Abbreviation: ICD-10, International Classification of Diseases—Tenth Edition.