Eur J Pediatr (2016) 175:71–80 DOI 10.1007/s00431-015-2590-9
ORIGINAL ARTICLE
Late detection of cleft palate K. H. Hanny 1 & I. A. C. de Vries 1 & S. J. Haverkamp 2 & K. P. Q. Oomen 3 & W. M. Penris 4 & M. J. C. Eijkemans 5 & M. Kon 1 & A. B. Mink van der Molen 1 & C. C. Breugem 1
Received: 30 January 2015 / Revised: 21 June 2015 / Accepted: 26 June 2015 / Published online: 1 August 2015 # The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract Cleft palate only (CPO) is a common congenital malformation, and most patients are diagnosed within the first weeks after birth. Late diagnosis of the cleft palate (CP) could initially result in feeding and growth impairment, and subsequently speech and hearing problems later in life. The purpose of this study is to retrospectively investigate (1) at which age CPO is diagnosed and (2) how the presence of syndromes and other factors relate to the age at diagnosis. The mean age of all children at our centre with CPO included between 1997 and 2014 at diagnosis (n = 271) was 1 year and 4 months. In all, 24.8 % (n=67) was older than 12 months when diagnosed, and 37.3 % (n=101) of all children had been diagnosed >30 days. These findings remain valid when a cut-off point of 14 days is used (44.3 %
Communicated by Jaan Toelen K.H. Hanny and I.A.C. de Vries are both first author. * I. A. C. de Vries [email protected] 1
Department of Paediatric Plastic Surgery, Wilhelmina Children’s Hospital, University Medical Centre, PO Box 85500, 3508 GA Utrecht, The Netherlands
2
Department of Speech and Language Therapy, Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, The Netherlands
3
Department of Otolaryngology-Head and Neck Surgery, Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, The Netherlands
4
Faculty of Behavioral and Social Sciences, University of Groningen, Groningen, The Netherlands
5
Department of Biostatistics and Research Support, Julius Centre, University Medical Centre, Utrecht, The Netherlands
late). Moreover, the grade of the cleft was a determining factor for successful diagnosis; submucous clefts were detected much later on average (89.3 %>30 days; p=.000). Similar results were found using Kaplan-Meier survival analyses. Conclusion: CPO is often diagnosed late. Patients diagnosed ≤30 days after birth more often presented with an associated disorder. Early diagnoses became more frequent as the severity of the cleft increased (grades 1–4). Professionals should perform more thorough intra-oral investigations, including manual palpations and visual inspections of the palate; they should be made more aware of the frequent accompanying symptoms. What is Known: • The presence of cleft palate only (CPO) is known to negatively affect feeding, hearing, speech and (social) development. • Submucous clefts are often underdiagnosed due to their difficulty to detect. As far as we know the literature shows that symptomatic submucous CPs are often diagnosed at an average age of 4.9 years. What is New: • 37.3 % respectively of all children with CPO were diagnosed relatively late (>30 days after birth), 24.8 % was older than 12 months when diagnosed. Mean age of all children with CPO was 1 year and 4 months. • We conclude that midwives and pediatricians should perform more through intra-oral investigations of all new-borns, including both a manual palpation, als well a visual inspection of the palate.
Keywords Cleft palate only . Diagnosis . Children . Age . Feeding difficulties . Nasal regurgitation
Abbreviations CI Confidence interval CL Cleft lip
72
CP CPO CPO+ CL/P CPT DCR df GA IQR NVSCA PRS SD SE VCF WCH WHO
Eur J Pediatr (2016) 175:71–80
Cleft palate Cleft palate only Cleft palate only with an associated disorder Cleft lip with palate Cleft palate team Dutch cleft registry Degrees of freedom Gestational age Interquartile range National Dutch Cleft Registry Pierre Robin sequence Standard deviation Standard error Velo-cardio-facial syndrome Wilhelmina Children’s Hospital World Health Organization
Introduction Oral clefts (OC) [25] frequently encountered craniofacial malformations and are generically divided into three groups: cleft lip (CL), cleft lip with cleft palate (CL/P), and cleft palate only (CPO). Depending on geographical location and racial ethnicity, the worldwide incidence of clefts is 1 in 1000 births for CL/P and 1 in 2000 births for CPO [25]; Asian ethnicity shows a higher incidence compared to Caucasian ethnicity, and African ethnicity shows the lowest incidence [25]. When looking at geographical location, at 13.50 in 10,000 births, the prevalence of CL/P in the Netherlands is higher than in all other European counties, except for Germany (13.94 in 10,000 births). Moreover, at 5.07 in 10,000 births, the prevalence of CPO in the Netherlands is relatively low as compared to the rest of Europe, especially as compared to Finland, which shows the highest European prevalence at 14.31 in 10,000 births [26]. The extent of CPO can range from a small indentation in the uvula (bifid uvula) to a complete cleft of the soft and hard palate [17]. Clefts of the palate are generally categorised into four grades (Fig. 1): grade 1, submucous cleft/bifid uvula; grade 2, soft palate only; grade 3, soft palate and 14 days) age at diagnosis. Finally, GA was also converted into a dichotomous variable: pre-term (12 months
9 67
3.3 % 24.8 %
75.2 % 100.0 %
≤14 days >14 days
151 120
55.7 % 44.3 %
55.7 % 100.0 %
≤30 days
170
62.7 %
62.7 %
>30 days Mean and SD (days)
101 502.49 and 1080.222
37.3 %
100.0 %
Mean and SD (patient X excluded) Median and IQR (days)
469.17 and 932.249 3.00 and 342.00
Extent of CP Of all 271 cases, Table 3 outlines that the most common type of cleft was grade 1 (27.7 %; n=75), while grade 2 was less common (23.2 %; n=63). Grade 3 occurred in 24.0 % (n=65), and finally grade 4 occurred in 25.1 % (n=68). Within the
Table 3
%
submucous group, 47 children had a bifid uvula (62.7 % of grade 1), and nine children (12.0 % of grade 1) were diagnosed with velopharyngeal insufficiency and/or hypoplasia of the palate. Though a cleft had not been detected in these eight patients, the typical CP symptoms of nasal regurgitation and hypernasality were present, and hypotonia/hypotrophy of the
Categorical variables of all included children with CPO Total 100 % (n=271)
Type of cleft 1. Submucous/bifid uvula 2. Soft palate only 3. Soft palate+partial hard palate 4. Complete cleft (soft+hard) Delivery location 1. Home 2. WCH 3. Hospital other than WCH 4. Abroad 5. Unknown Syndromic CP (CPO+) 1. Yes 2. No GA cut-off (weeks) 1. Pre-term (30 days 37.3 % (n=101)
89.3 (n=67) 34.9 (n=22) 10.8 (n=7) 7.4 (n=5) 36.8 (n=25) 19.5 (n=8) 39.4 (n=56) 66.6 (n=2) 58.8 (n=10) 30.2 (n=38) 43.4 (n=63)
≤14 days 55.7 % (n=151) p=0.000 8.0 (n=6) 54.0 (n=34) 81.5 (n=53) 85.3 (n=58) p=0.003 57.4 (n=39) 73.2 (n=30) 54.9 (n=78) 33.3 (n=1) 17.6 (n=3) p=0.002 65.9 (n=83) 46.9 (n=68)
> 14 days 44.3 % (n=120)
92.0 (n=69) 46.0 (n=29) 18.5 (n=12) 14.7 (n=10) 42.6 (n=29) 26.8 (n=11) 45.1 (n=64) 66.6 (n=2) 82.4 (n=14) 34.1 (n=43) 53.1 (n=77)
Eur J Pediatr (2016) 175:71–80
75
velar muscles had been diagnosed. Two of these eight patients were diagnosed with velo-cardio-facial syndrome (VCF). Of the patients diagnosed late (>30 days), most had a submucous cleft (66.3 %; n=67), and as the severity of the cleft increased, late detection occurred less often: within 30 days, 22 grade 2 patients were diagnosed, seven grade 3 patients and five grade 4 patients. A chi-squared test revealed a highly significant association between the grade of the cleft (1–4) and the age at diagnosis (≤30 days (early)/>30 days (late); p=.000); as the severity of the CP increased, the chances of early diagnosis also increased. Early diagnosis occurred most frequently in children with a grade 4 CP (92.6 % of grade 4; n=63), while late diagnosis was common in grade 1 patients (89.3 % of grade 1; n=67). Similar results are visible when early age at diagnosis was set at ≤14 days (p=.000). Associated disorders Pierre Robin sequence (PRS) generally consists of a triad of symptoms entailing micrognathia, glossoptosis and the resulting post-partum respiratory distress [5]. Although there currently is no global consensus on the exact definition of PRS, there is a well-known common concomitance of CP [4]. Over 80 % of children with PRS eventually displays an associated syndrome such as, e.g. Stickler syndrome or VCF (22q11) [23]. Of all 271 cases, 46.5 % (n=126) was classified as having an associated disorder (CPO+). Table 4 outlines that the majority of this group was diagnosed with PRS without
Table 4 Syndromic and/or congenital abnormalities of all included children with CPO Syndromic and/or congenital abnormalities of all included children CP+ Total % (n=126) PRS PRS with Stickler PRS with VCFS/22q11 PRS with Treacher-Collins CPO+ without clear diagnosis/syndrome CHARGE syndrome Kabuki syndrome Trisomy 21 18q-syndrome Van der Woude syndrome 4q-, 13q-, 19q-, Auriculocondylar-, Beckwith Wiedeman-, BOR-, EEC-, Klippel Feil-, Loeys-Dietz-, Moebius-, DOOR-, orodigital-facial-, SEDH-, Adams Oliver-, Apert-, Goldenhar-, Rieger-, Triple X-, Worster Drought syndrome ODS type 1, partial diprosopus, inversion duplication chromosome 15, hemifascial microsomy
40.5 % (n=51) 14.3 % (n=18) 11.9 % (n=15) 0.8 % (n=1) 4.0 % (n=5) 2.4 % (n=3) 2.4 % (n=3) 1.6 % (n=2)
0.8 % (n=1)
0.8 % (n=1)
any associated disorders (40.5 %; n=51). It is noteworthy that all 51 patients suffered from PRS with CP. Of all 126 CPO+ patients, 14.3 % (n=18) was diagnosed with Stickler’s and 11.9 % (n=15) with VCF (22q11). Moreover, there was a large variety of other syndromes, summarised in Table 4. Visible in Table 3, a chi-squared test revealed a significant association between the presence of associated disorders (yes/ no) and the age at diagnosis (≤30 days (early)/>30 days (late); p=.024); in the late diagnosis group, CPO+ was less frequently diagnosed. Similar results are visible when early age at diagnosis was set at ≤14 days (p30 days (late); p=.036). Since 62.7 % (n=170) of all cases were diagnosed early regardless of location, early detections occurred roughly evenly frequently in home settings (63.2 %) and non-WCH hospital settings (60.6 %). Early detection did occur more frequently at the WCH (80.5 %). Similar results are visible when Bearly^ was defined as ≤14 days (p30 days; 33.3 %). Of these ten late-diagnosed children, 60.0 % (n=6) had a grade 1 CP, 20.0 % (n = 2) had a grade 2 CP and 20.0 % (n=2) had a grade 3 CP. There were no premature children with a late-diagnosed grade 4 CP (p=.001). With Blate^ defined as >14 days, results were similar: in the early group, there were 6 grade 1 patients (54.5 %), 2 grade 2 patients (33.3 %), 2 grade 3 patients (33.3 %) and 1 grade 4 patient (11.1 %; p=.003). Finally, of all included children with CPO, 7.4 % (n=20) had an unknown GA, because the information could not be retrieved from the (relevant) medical records. Table 5 Kaplan-Meier survival analyses of age at diagnosis (days)
Survival analyses In addition to the previous chi-squared analyses, several Kaplan-Meier survival analyses were conducted to compare (log rank test) the age at diagnosis with the categorical variables, resulting in Table 5. First, for cleft type, grade 1 patients had a much higher median age at diagnosis (1282 days) than grade 2 patients (12 days), who, in turn, had a higher median age than grades 3 and 4 patients (0 and 0 days, respectively; p
ORIGINAL ARTICLE
Late detection of cleft palate K. H. Hanny 1 & I. A. C. de Vries 1 & S. J. Haverkamp 2 & K. P. Q. Oomen 3 & W. M. Penris 4 & M. J. C. Eijkemans 5 & M. Kon 1 & A. B. Mink van der Molen 1 & C. C. Breugem 1
Received: 30 January 2015 / Revised: 21 June 2015 / Accepted: 26 June 2015 / Published online: 1 August 2015 # The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract Cleft palate only (CPO) is a common congenital malformation, and most patients are diagnosed within the first weeks after birth. Late diagnosis of the cleft palate (CP) could initially result in feeding and growth impairment, and subsequently speech and hearing problems later in life. The purpose of this study is to retrospectively investigate (1) at which age CPO is diagnosed and (2) how the presence of syndromes and other factors relate to the age at diagnosis. The mean age of all children at our centre with CPO included between 1997 and 2014 at diagnosis (n = 271) was 1 year and 4 months. In all, 24.8 % (n=67) was older than 12 months when diagnosed, and 37.3 % (n=101) of all children had been diagnosed >30 days. These findings remain valid when a cut-off point of 14 days is used (44.3 %
Communicated by Jaan Toelen K.H. Hanny and I.A.C. de Vries are both first author. * I. A. C. de Vries [email protected] 1
Department of Paediatric Plastic Surgery, Wilhelmina Children’s Hospital, University Medical Centre, PO Box 85500, 3508 GA Utrecht, The Netherlands
2
Department of Speech and Language Therapy, Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, The Netherlands
3
Department of Otolaryngology-Head and Neck Surgery, Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, The Netherlands
4
Faculty of Behavioral and Social Sciences, University of Groningen, Groningen, The Netherlands
5
Department of Biostatistics and Research Support, Julius Centre, University Medical Centre, Utrecht, The Netherlands
late). Moreover, the grade of the cleft was a determining factor for successful diagnosis; submucous clefts were detected much later on average (89.3 %>30 days; p=.000). Similar results were found using Kaplan-Meier survival analyses. Conclusion: CPO is often diagnosed late. Patients diagnosed ≤30 days after birth more often presented with an associated disorder. Early diagnoses became more frequent as the severity of the cleft increased (grades 1–4). Professionals should perform more thorough intra-oral investigations, including manual palpations and visual inspections of the palate; they should be made more aware of the frequent accompanying symptoms. What is Known: • The presence of cleft palate only (CPO) is known to negatively affect feeding, hearing, speech and (social) development. • Submucous clefts are often underdiagnosed due to their difficulty to detect. As far as we know the literature shows that symptomatic submucous CPs are often diagnosed at an average age of 4.9 years. What is New: • 37.3 % respectively of all children with CPO were diagnosed relatively late (>30 days after birth), 24.8 % was older than 12 months when diagnosed. Mean age of all children with CPO was 1 year and 4 months. • We conclude that midwives and pediatricians should perform more through intra-oral investigations of all new-borns, including both a manual palpation, als well a visual inspection of the palate.
Keywords Cleft palate only . Diagnosis . Children . Age . Feeding difficulties . Nasal regurgitation
Abbreviations CI Confidence interval CL Cleft lip
72
CP CPO CPO+ CL/P CPT DCR df GA IQR NVSCA PRS SD SE VCF WCH WHO
Eur J Pediatr (2016) 175:71–80
Cleft palate Cleft palate only Cleft palate only with an associated disorder Cleft lip with palate Cleft palate team Dutch cleft registry Degrees of freedom Gestational age Interquartile range National Dutch Cleft Registry Pierre Robin sequence Standard deviation Standard error Velo-cardio-facial syndrome Wilhelmina Children’s Hospital World Health Organization
Introduction Oral clefts (OC) [25] frequently encountered craniofacial malformations and are generically divided into three groups: cleft lip (CL), cleft lip with cleft palate (CL/P), and cleft palate only (CPO). Depending on geographical location and racial ethnicity, the worldwide incidence of clefts is 1 in 1000 births for CL/P and 1 in 2000 births for CPO [25]; Asian ethnicity shows a higher incidence compared to Caucasian ethnicity, and African ethnicity shows the lowest incidence [25]. When looking at geographical location, at 13.50 in 10,000 births, the prevalence of CL/P in the Netherlands is higher than in all other European counties, except for Germany (13.94 in 10,000 births). Moreover, at 5.07 in 10,000 births, the prevalence of CPO in the Netherlands is relatively low as compared to the rest of Europe, especially as compared to Finland, which shows the highest European prevalence at 14.31 in 10,000 births [26]. The extent of CPO can range from a small indentation in the uvula (bifid uvula) to a complete cleft of the soft and hard palate [17]. Clefts of the palate are generally categorised into four grades (Fig. 1): grade 1, submucous cleft/bifid uvula; grade 2, soft palate only; grade 3, soft palate and 14 days) age at diagnosis. Finally, GA was also converted into a dichotomous variable: pre-term (12 months
9 67
3.3 % 24.8 %
75.2 % 100.0 %
≤14 days >14 days
151 120
55.7 % 44.3 %
55.7 % 100.0 %
≤30 days
170
62.7 %
62.7 %
>30 days Mean and SD (days)
101 502.49 and 1080.222
37.3 %
100.0 %
Mean and SD (patient X excluded) Median and IQR (days)
469.17 and 932.249 3.00 and 342.00
Extent of CP Of all 271 cases, Table 3 outlines that the most common type of cleft was grade 1 (27.7 %; n=75), while grade 2 was less common (23.2 %; n=63). Grade 3 occurred in 24.0 % (n=65), and finally grade 4 occurred in 25.1 % (n=68). Within the
Table 3
%
submucous group, 47 children had a bifid uvula (62.7 % of grade 1), and nine children (12.0 % of grade 1) were diagnosed with velopharyngeal insufficiency and/or hypoplasia of the palate. Though a cleft had not been detected in these eight patients, the typical CP symptoms of nasal regurgitation and hypernasality were present, and hypotonia/hypotrophy of the
Categorical variables of all included children with CPO Total 100 % (n=271)
Type of cleft 1. Submucous/bifid uvula 2. Soft palate only 3. Soft palate+partial hard palate 4. Complete cleft (soft+hard) Delivery location 1. Home 2. WCH 3. Hospital other than WCH 4. Abroad 5. Unknown Syndromic CP (CPO+) 1. Yes 2. No GA cut-off (weeks) 1. Pre-term (30 days 37.3 % (n=101)
89.3 (n=67) 34.9 (n=22) 10.8 (n=7) 7.4 (n=5) 36.8 (n=25) 19.5 (n=8) 39.4 (n=56) 66.6 (n=2) 58.8 (n=10) 30.2 (n=38) 43.4 (n=63)
≤14 days 55.7 % (n=151) p=0.000 8.0 (n=6) 54.0 (n=34) 81.5 (n=53) 85.3 (n=58) p=0.003 57.4 (n=39) 73.2 (n=30) 54.9 (n=78) 33.3 (n=1) 17.6 (n=3) p=0.002 65.9 (n=83) 46.9 (n=68)
> 14 days 44.3 % (n=120)
92.0 (n=69) 46.0 (n=29) 18.5 (n=12) 14.7 (n=10) 42.6 (n=29) 26.8 (n=11) 45.1 (n=64) 66.6 (n=2) 82.4 (n=14) 34.1 (n=43) 53.1 (n=77)
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75
velar muscles had been diagnosed. Two of these eight patients were diagnosed with velo-cardio-facial syndrome (VCF). Of the patients diagnosed late (>30 days), most had a submucous cleft (66.3 %; n=67), and as the severity of the cleft increased, late detection occurred less often: within 30 days, 22 grade 2 patients were diagnosed, seven grade 3 patients and five grade 4 patients. A chi-squared test revealed a highly significant association between the grade of the cleft (1–4) and the age at diagnosis (≤30 days (early)/>30 days (late); p=.000); as the severity of the CP increased, the chances of early diagnosis also increased. Early diagnosis occurred most frequently in children with a grade 4 CP (92.6 % of grade 4; n=63), while late diagnosis was common in grade 1 patients (89.3 % of grade 1; n=67). Similar results are visible when early age at diagnosis was set at ≤14 days (p=.000). Associated disorders Pierre Robin sequence (PRS) generally consists of a triad of symptoms entailing micrognathia, glossoptosis and the resulting post-partum respiratory distress [5]. Although there currently is no global consensus on the exact definition of PRS, there is a well-known common concomitance of CP [4]. Over 80 % of children with PRS eventually displays an associated syndrome such as, e.g. Stickler syndrome or VCF (22q11) [23]. Of all 271 cases, 46.5 % (n=126) was classified as having an associated disorder (CPO+). Table 4 outlines that the majority of this group was diagnosed with PRS without
Table 4 Syndromic and/or congenital abnormalities of all included children with CPO Syndromic and/or congenital abnormalities of all included children CP+ Total % (n=126) PRS PRS with Stickler PRS with VCFS/22q11 PRS with Treacher-Collins CPO+ without clear diagnosis/syndrome CHARGE syndrome Kabuki syndrome Trisomy 21 18q-syndrome Van der Woude syndrome 4q-, 13q-, 19q-, Auriculocondylar-, Beckwith Wiedeman-, BOR-, EEC-, Klippel Feil-, Loeys-Dietz-, Moebius-, DOOR-, orodigital-facial-, SEDH-, Adams Oliver-, Apert-, Goldenhar-, Rieger-, Triple X-, Worster Drought syndrome ODS type 1, partial diprosopus, inversion duplication chromosome 15, hemifascial microsomy
40.5 % (n=51) 14.3 % (n=18) 11.9 % (n=15) 0.8 % (n=1) 4.0 % (n=5) 2.4 % (n=3) 2.4 % (n=3) 1.6 % (n=2)
0.8 % (n=1)
0.8 % (n=1)
any associated disorders (40.5 %; n=51). It is noteworthy that all 51 patients suffered from PRS with CP. Of all 126 CPO+ patients, 14.3 % (n=18) was diagnosed with Stickler’s and 11.9 % (n=15) with VCF (22q11). Moreover, there was a large variety of other syndromes, summarised in Table 4. Visible in Table 3, a chi-squared test revealed a significant association between the presence of associated disorders (yes/ no) and the age at diagnosis (≤30 days (early)/>30 days (late); p=.024); in the late diagnosis group, CPO+ was less frequently diagnosed. Similar results are visible when early age at diagnosis was set at ≤14 days (p30 days (late); p=.036). Since 62.7 % (n=170) of all cases were diagnosed early regardless of location, early detections occurred roughly evenly frequently in home settings (63.2 %) and non-WCH hospital settings (60.6 %). Early detection did occur more frequently at the WCH (80.5 %). Similar results are visible when Bearly^ was defined as ≤14 days (p30 days; 33.3 %). Of these ten late-diagnosed children, 60.0 % (n=6) had a grade 1 CP, 20.0 % (n = 2) had a grade 2 CP and 20.0 % (n=2) had a grade 3 CP. There were no premature children with a late-diagnosed grade 4 CP (p=.001). With Blate^ defined as >14 days, results were similar: in the early group, there were 6 grade 1 patients (54.5 %), 2 grade 2 patients (33.3 %), 2 grade 3 patients (33.3 %) and 1 grade 4 patient (11.1 %; p=.003). Finally, of all included children with CPO, 7.4 % (n=20) had an unknown GA, because the information could not be retrieved from the (relevant) medical records. Table 5 Kaplan-Meier survival analyses of age at diagnosis (days)
Survival analyses In addition to the previous chi-squared analyses, several Kaplan-Meier survival analyses were conducted to compare (log rank test) the age at diagnosis with the categorical variables, resulting in Table 5. First, for cleft type, grade 1 patients had a much higher median age at diagnosis (1282 days) than grade 2 patients (12 days), who, in turn, had a higher median age than grades 3 and 4 patients (0 and 0 days, respectively; p
