or palate in 701,181 Japanese people

Survey of congenital anomalies associated with cleft lip and/or palate in 701,181 Japanese people Nagato Natsume, DDS, DMedSc, PhD,a Teruyuki Niimi, DDS, PhD,b Hiroo Furukawa DDS, PhD,b Toshihiko Kawai, DDS, PhD,c Nobumi Ogi DDS, PhD,c Yasushi Suzuki, DDS,d and Tsuyoshi Kawai, DDS, PhD,e Nagoya, Japan AICHI-GAKUIN UNIVERSITY

There have been many reports on congenital anomalies associated with cleft lip and/or palate (CL/CLP) in Japan. However, these reports included data only on patients who came to hospitals; thus the real situation regarding these anomalies remains unclear. Therefore, we surveyed newborns at all delivery facilities in the central area of Japan for the presence of these anomalies, following their progress for 12 consecutive years; at the end of that time, questionnaires were collected and analyzed. In this article, we describe our results. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:157-61)

Numerous reports of congenital anomalies associated with cleft lip and/or palate (CL/CLP) have appeared.1-3 However, the prevalence among the general public remains unclear because most reports record only the total number of patients in hospitals. This report describes various cases of congenital anomalies associated with CL/CLP recorded from 1982 to 1994 in all child-delivery facilities in the Tokai area, in the central part of the main island of Japan.

METHOD Each delivery facility in the Tokai area informed us annually of its number of births, from which we conducted a survey of babies born with CL/CLP. This survey recorded the month of birth, sex, birth weight, and associated congenital anomalies of every baby with CL/CLP. The survey period was 12 years and covered 701,181 births, which accounted for 53.7% of the 1,305,030 births in this area. The main subjects of this survey were 1063 newborns with CL/CLP. Some birth weight records or details about the associated congenital anomalies were insufficient because each delivery facility aProfessor, The Second Department of Oral and Maxillofacial Surgery, School of Dentistry, and The Cleft Lip and Palate Center, Aichi-Gakuin University. bAssistant Professor, The Second Department of Oral and Maxillofacial Surgery, School of Dentistry, and The Cleft Lip and Palate Center, Aichi-Gakuin University. cAssociate Professor, The Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University. dPostgraduate Student, The Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University. eEmeritus Professor, The Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University. Received for publication Jun 5, 2000; returned for revision Aug 3, 2000; accepted for publication Oct 31, 2000. Copyright © 2001 by Mosby, Inc. 1079-2104/2001/$35.00 + 0 7/12/112948 doi:10.1067/moe.2001.112948

used a slightly different nomenclature; further inquiries were unsuccessful, given that, to protect their privacy, patients’ names and addresses were not recorded.

RESULTS Table I provides an incidence order of the congenital anomalies. Cleft lip Cleft lip (CL) was observed in 362 (34.1%) of the 1063 CL/CLP births. Associated congenital anomalies were observed in 37 (11.4%) of 324 births, which included newborns whose cleft type and sex were recorded and excluded newborns whose associated congenital anomalies were of an unknown type. Table II lists the congenital anomalies associated with CL. Cleft lip and palate Cleft lip and palate (CLP) was observed in 483 (45.4%) of the 1063 CL/CLP births. Associated congenital anomalies were observed in 65 (16.2%) of 402 births, which included newborns whose cleft type and sex were recorded and excluded newborns whose associated congenital anomalies were of an unknown type (Table III). Cleft palate Cleft palate (CP) was observed in 218 (20.5%) of the 1063 CL/CLP births. Associated congenital anomalies were observed in 39 (20.7%) of 188 births, which included newborns whose cleft type and sex were recorded and excluded newborns whose associated congenital anomalies were of an unknown type (Table IV). DISCUSSION Although cases of congenital anomalies associated with CL/CLP have been reported by many hospitals, 157

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Table I. Congenital anomalies Incidence order 1 2 3 3 5 5 7 7 9 9 9 9 9 14 14 14 14 14 14 14 14 14 14 14 14 14 14 28

Congenital anomaly CL/CLP Down syndrome VSD Hydrocephaly Diaphragmatic hernia Spina bifida CL Esophageal atresia Polydactyly (finger): radial Syndactyly (finger): ulnar Cerebral hernia Omphalocele Hypospadias Polydactyly (finger): ulnar Polydactyly (finger): unknown Syndactyly (toe): central Syndactyly (toe): fibular Low-set ear Malformed ear Pilonidal sinus Tracheoesophageal fistula Congenital constriction ring syndrome PDA Left ventricular hypoplasia Polycystic dysplasia Duodenal/intestinal atresia Malrotation of intestine Polydactyly (toe): tibial

Incidence order 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 55 54

Congenital anomaly Polydactyly (toe): unknown Ectrodactyly (finger): central Reduction defects of upper limb: central Reduction defects of upper limb: ulnar Reduction defects of lower limb: tibial Absent nail Brachymelia: upper limb Brachymelia: lower limb Cleft foot Facial fissure Mandibular micrognathia Microtia Absence of earlobe Anencephaly Gastroschisis Anal atresia Anal heterotopia Fistula in external genital area Gynatresia Urethral atresia Renal aplasia/dysplasia Arthrogryposis multiplex congenita Transposition of great arteries Aortic stenosis Tetralogy of Fallot Multiple congenital anomalies Other congenital heart defects Other

VSD, Ventricular septal defects; PDA, patent ductus arteriosus.

the data differ among hospitals. For example, many cases were from general hospitals that have neonatal intensive care units, whereas few patients with associated anomalies are introduced to the dental hospitals attached to universities like ours. Therefore, we investigated associated congenital anomalies in Japan by surveying child-delivery facilities. Although this method is effective for studying spontaneous associated anomalies, it is difficult for obstetricians to classify diseases such as cardiac anomalies or diagnose subcutaneous CP without long-term follow-up. Another problem is that, to protect the privacy of patients and their families, some volunteer groups refuse to monitor the nature of birth defects. Therefore, we monitor congenital anomalies while taking care not to reveal any patient’s identity. As a result, some of our survey results are unclear or different from surveyor to surveyor. Despite this, we recognize the importance of protecting patients’ privacy from an ethical standpoint. Table I shows common abnormalities in Japanese people. Among congenital anomalies in the Japanese, CLP is the most common, followed by heart, cerebral, or finger anomalies, as well as CL. However, in Japan

there has been no large-scale investigation of congenital anomalies associated with CL/CLP. The incidence of congenital anomalies associated with CL (11.4%), CL/CLP (16.2%), and CP (20.7%) in our survey of more than 700,000 Japanese people differed from those of previous studies of congenital anomalies in the Japanese.4-7 This discrepancy in the findings needs to be studied further. Our findings did not include subcutaneous CP, which would have been included if we had surveyed treatment facilities. We will continue to monitor the change in congenital anomalies in this area, which has a total population of 11 million people. REFERENCES 1. Milerad J, Larson O, Hagberg C, Ideberg M. Associated malformations in infants with cleft lip and palate: a prospective, population-based study. Pediatrics 1997;100:180-6. 2. Stoll C, Alembik Y, Dott B, Roth MP. Epidemiological and genetic study in 207 cases of oral clefts in Alsace, north-eastern France. J Med Genet 1991;28:325-9. 3. Kernahan DA, Stark RB. A new classification for cleft lip and cleft palate. Plast Reconstr Surg 1958;22:435-41. 4. Natsume N, Kawai T. Incidence of cleft lip and palate in 39,606 Japanese babies born during 1983. Int J Oral Maxillofac Surg 1986;15:565-8.

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Table II. Congenital anomalies associated with CL Male Body weight (g) 1520 2052 2188 2450 2450 2500 2606 2706 2780 2898 2940 2970 3150 3245 3300 3620 3770 3944 2080 1962 2346 unknown unknown

Female Associated anomaly

Multiple congenital anomalies DORV Treacher Collins syndrome Immunodeficiency syndrome Immunodeficiency syndrome Microphthalmos Pierre Robin syndrome Polydactyly Pierre Robin syndrome, auricular defect Blepharo accretion Gastric perforation Roberts’ syndrome Biliary atresia Hypervolemia Ectrodactyly (finger) Pierre Robin syndrome, auricular defect Polydactyly (finger) Hypospadias, syndactyly (toe) Other Other Other Other Other

DORV, Double outlet right ventricle. Average body weight, male: 2737.0 g (with associated anomalies) Average body weight, female: 2508.0 g (with associated anomalies) Average body weight, male: 3108.3 g (without associated anomalies) Average body weight, female: 2940.3 g (without associated anomalies)

Body weight (g) 1968 2150 2280 2370 2430 2510 2860 3120 3364 unknown unknown 2028 unknown

Associated anomaly Polydactyly (finger) Down syndrome Congenital heart defect Other Trisomy 13 Microcephaly Fistula of lip Premature beat Trisomy 18 Accessory ear Anencephaly Other Other

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Table III. Congenital anomalies associated with CLP Male Body weight (g) 1200 1300 1512 1560 1700 2010 2058 2196 2292 2400 2670 2828 2960 3006 3030 3100 3131 3212 3280 3288 3342 3810 3900 4090 1756 1820 2470 2518 unknown unknown unknown

Female Associated anomaly

Alveolar hypoplasia Diaphragmatic hernia, ectrodactyly (finger) Multiple congenital anomalies Trisomy 18 Hydrocephaly, syndactyly, ectrodactyly Polydactyly Heart anomaly, syndactyly Multiple congenital anomalies DORV, VSD Polydactyly, tracheoesophageal fistula Holoprosencephaly Goldenhar’s syndrome, tetralogy of Fallot Cardiac disease Syndactyly VSD Heart defect Syndactyly (toe) Diaphragmatic hernia, ASD, VSD, PDA Abnormal venous return VSD MSA Accessory ear Pes varus Pneumothorax Other Other Other Other Cerebral anomaly Hypospadias Other

ASD, Atrial septal defect; MSA, multiple system atrophy. Average body weight, male: 2587.1 g (with associated anomalies) Average body weight, female: 2375.1 g (with associated anomalies) Average body weight, male: 3072.2 g (without associated anomalies) Average body weight, female: 3058.3 g (without associated anomalies)

Body weight (g) 992 1126 1366 1550 1670 1730 1830 1950 2040 2160 2166 2266 2266 2314 2484 2620 2662 2720 2810 2920 2930 2955 3100 3146 3260 3370 3460 2640 unknown unknown unknown

Associated anomaly Multiple congenital anomalies Hydrocephaly Chromosomal aberration Multiple congenital anomalies Trisomy E Patent ductus arteriosus Goldenhar’s syndrome Trisomy 18 VSD Ectrodactyly (finger, toe) Posterior nasal stenosis Trisomy 18 Duodenal atresia Anomalies of ear and eye DORV Cardiac anomaly Polydactyly ASD Pes varus Dandy-Walker syndrome VSD Malformed ear Down syndrome, polydactyly ASD, VSD, PDA VSD ASD Respiratory disorder Other Atelectasis Malformed ear Congenital heart anomaly

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Table IV. Congenital anomalies associated with CP Male Body weight (g) 1194 1745 2180 2380 2452 2598 2730 3090 3130 3230 3336 3344 3444 3510 2548 3036 unknown

Female Associated anomaly

Syndactyly, diaphragmatic hernia, VSD, ectrodactyly (finger) Syndactyly Pierre Robin syndrome Multiple congenital anomalies PB, low-set ear, duodenal atresia Pes varus Heart defect Blepharoptosis Treacher Collins syndrome Pierre Robin syndrome Down syndrome Pierre Robin syndrome Low-set ear Heart defect Cataract, hypospadias, tetralogy of Fallot Other Chromosomal aberration

Body weight (g) 2400 1930 2182 2190 2360 2388 1364 2430 2478 2690 2744 2860 2940 2946 3040 3130 3230 3310 3356 4025 unknown 2860

Associated anomaly Pierre Robin syndrome, chromosomal aberration Esophageal atresia Eyeball anomaly Rubinstein-Taybi syndrome Pierre Robin syndrome, heart defect Hydrocephaly Chylothorax Subarachnoid hemorrhage Pierre Robin syndrome Pierre Robin syndrome Pierre Robin syndrome Pierre Robin syndrome Pierre Robin syndrome Auricle defect Exophthalmos, low-set ear Pierre Robin syndrome, micromelia Pierre Robin syndrome Hydrocephaly Pierre Robin syndrome Pierre Robin syndrome Alveolar cleft Other

Average body weight, male: 2746.7 g (with associated anomalies) Average body weight, female: 2707.3 g (with associated anomalies) Average body weight, male: 3163.2 g (without associated anomalies) Average body weight, female: 3020.9 g (without associated anomalies)

5. Natsume N. Incidence of cleft lip and palate among Japanese newborns 1982 to 1984. Plast Reconstr Surg 1987;79:499-501. 6. Natsume N, Suzuki T, Kawai T. The prevalence of cleft lip and palate in the Japanese: Their birth prevalence in 40,304 infants born during 1982. Oral Surg Oral Med Oral Pathol 1987;63: 421-3. 7. Natsume N, Suzuki T, Kawai T. The prevalence of cleft lip and palate in Japanese. Br J Oral Maxillofac Surg 1988;26: 232-6.

Reprint requests: Nagato Natsume, DDS, DMedSc, PhD Second Department of Oral and Maxillofacial Surgery School of Dentistry Aichi-Gakuin University 1-22, Suemori-dori, Chikusa-ku Nagoya, Japan 464-8651 [email protected]