Epidemiology of Cleft Lip and Cleft Palate in Pakistan

Epidemiology of Cleft Lip and Cleft Palate in Pakistan Mohammed Mehboob Elahi, M.D., M.Sc., Ian T. Jackson, M.D., Omar Elahi, M.B.B.S., Ayesha H. Khan, M.B.B.S., Fatima Mubarak, M.B.B.S., Gul Bano Tariq, M.B.B.S., and Amit Mitra, M.D. Philadelphia, Pa.; Southfield, Mich.; Abbotabad and Peshawar, Northwest Frontier Province, and Lahore, Punjab, Pakistan Clinical and epidemiologic studies of defined geographic populations can serve as a means of establishing data important for the diagnosis, treatment, and counseling of patients with cleft lip and cleft palate. Several descriptive epidemiologic studies have been carried out in many countries worldwide; however, no such study has ever been performed in Pakistan. Population-based data on the incidence of cleft lip and palate were obtained from birth registry information in northern Pakistan. A total of 117 cases from 61,156 live births reported were identified. The incidence for cleft lip and/or cleft palate was 1.91 per 1000 births (one per 523 births). Cleft lip alone (42 percent) was noted more frequently than isolated cleft palate (24 percent) and combined cleft lip and palate deformities (34 percent). Boys were more commonly affected by cleft lip and cleft lip with cleft palate, whereas girls predominated in the isolated cleft palate cases. Consanguineous marriages were observed in 32 percent of parents versus 18 percent in matched controls. Only 32 percent of cleft mothers received formal prenatal counseling, monthly examinations, and regular laboratory testing during the entirety of the pregnancy. Nutritional and vitamin supplements were given to only 28 percent of mothers of cleft children versus 59 percent in matched controls. Descriptive statistics were used to assess pertinent risk factors associated with cleft lip and palate. The acquisition of incidence and associated data has generated baseline information on the magnitude of cleft lip and cleft palate in Pakistan. It is hoped that this information can be used for appropriate resource use, cleft lip and cleft palate prevention programs, and counseling programs with Pakistan-specific data. (Plast. Reconstr. Surg. 113: 1548, 2004.) chological concerns. With increases in world population and parallel increases in life expectancy, the numbers of people living with orofacial clefts will increase. The majority of cleft lips and/or cleft palates are believed to be caused by the multifactorial inheritance of a threshold character, whereby several genes act in concert with environmental agents.2 The relative contributions of these genetic and environmental influences have been repeatedly examined in a number of investigations.2–7 Nevertheless, the exploration of demographic variables in different populations throughout the world has had the greatest impact in advancing our understanding of orofacial clefts. The incidence at birth is acknowledged at one in 500 to one in 1000, varying by race, geographic location, sex, and nationality.8 Asians are at higher risk than whites or blacks.2,8 Significant differences exist, however, across and within racial, ethnic, and national boundaries that underscore the importance of obtaining distinct subsets of data in different regions of the world. Descriptive epidemiologic studies on cleft lip and cleft palate have been carried out in several countries worldwide.9 –12 No such study, however, has ever been performed in Pakistan. According to extrapolated statistics published by the Smile Train (New York, N.Y.), it is believed that Pakistan has the fourth largest number of cleft births in the world, behind China, India, and Indonesia. Pakistan is a strategically positioned country Cleft lip and cleft palate are problems of immense international proportions, affecting in excess of 10 million people worldwide.1 As the most common congenital malformation of the head and neck region, its appearance is heralded by a unique set of physical and psy- From the Division of Plastic and Reconstructive Surgery, Temple University; Institute for Craniofacial and Reconstructive Surgery; Division of Plastic Surgery, Providence Hospital; Ayub Medical College; Khyber University Teaching Hospital; and King Edward Medical College. Received for publication May 9, 2003; revised June 24, 2003. DOI: 10.1097/01.PRS.0000117184.77459.2B 1548 Vol. 113, No. 6 / EPIDEMIOLOGY OF CLEFT LIP AND PALATE that bridges the Middle East and the rest of Asia. It is a complex multiethnic society of 140 million people whose cultural roots range from Greece, Turkey, and the Arabian peninsula to Persia, Mongolia, and India. The development of natural gas, oil, and mineral deposits and the growth of the textile industry, manufacturing, and information technology are among factors that are influencing the rate of Pakistan’s economic growth. Nevertheless, growth has been uneven, and widespread poverty persists. Pakistan ranks 134th of the 173 countries on the United Nations Development Program’s human development index; at least 35 million people live in conditions of abject poverty.13 In Pakistan, as is true in many developing countries, the scarcity of reliable epidemiologic information on the extent of a health problem is a major cause of neglect. This study was designed with the intent of providing preliminary population-based data on the incidence of cleft lip and cleft palate and to identify factors associated with their development. PATIENTS AND METHODS The study was conducted in the Northwest Frontier Province of Pakistan in both a retrospective and a prospective fashion. Birth and population data obtained from the provincial birth registry in the city of Abbotabad were reviewed for cases of cleft lip and cleft palate. Abbotabad is a hill station town that houses several military regimental headquarters. The health facilities are relatively sophisticated by Pakistani standards and have a well-organized 1549 central birth registry. However, a significant portion of children are born outside of the hospital system, with estimates ranging from 45 to 55 percent.13 Bearing in mind that calculated incidence data were based on total birth figures in the centers sampled (coinciding with the location of reported cases of cleft lip and/or cleft palate), we feel that meaningful data were collected. Retrospective analysis from January 1, 1998, to December 31, 2001, was performed. Cases were selected by searching for and identifying the key word “cleft” from all birth records. Concurrently, an active count of children born with cleft lip and cleft palate was maintained for a 6-month period from January 1, 2002, to June 30, 2002. The study generated data over a 4.5-year time span, reducing the possibility of random variations, to provide a more representative data sample. Cases of cleft lip and/or cleft palate were registered by name, sex, and father’s name. Physical examination of these children was performed and the cleft described according to Smith’s modification of Kernahan’s “Y” classification.14,15 This classification system was used for all cleft cases, and a stamped symbolic representation, appropriately filled out for the type of cleft anomaly, was included in patient charts (Fig. 1). The symbolic representation allows for the inclusion of the full spectrum of cleft abnormalities in an easy-to-use format that is readily amenable to data collection and tabulation (Fig. 2).15 Related congenital anomalies, if present, were also noted. Controls were matched to the cases of cleft FIG. 1. Smith et al. modification of the Kerhahan Y system to classify cleft lip and cleft palate deformities. From Ahuja, R. B. Primary definitive nasal correction in patients presenting for late unilateral cleft lip repair. Plast. Reconstr. Surg. 110: 17, 2002. 1550 PLASTIC AND RECONSTRUCTIVE SURGERY, May 2004 childbirth complications, maternal and child immunization history, trauma, teratogen or environmental exposures, birth order, and other contributing information. The acquired data were entered into a computerized database and analyzed. Incidence was calculated as the number of new cases in the total population studied. Descriptive statistics were used to analyze the various risk factors and demographic variables related to orofacial clefting. RESULTS FIG. 2. Example of a complete left-sided cleft lip and palate characterized by the Smith et al. modification of the Kerhahan Y classification. From Ahuja, R. B. Primary definitive nasal correction in patients presenting for late unilateral cleft lip repair. Plast. Reconstr. Surg. 110: 17, 2002. lip and/or cleft palate on the basis of available age, sex, and related demographic variables to obtain information on cleft association. Controls were selected from the same villages of families with socioeconomic standing comparable to the cleft patients. The orofacial cleft cases and the control groups were then administered a cleft lip/cleft palate Risk Factor Survey to specifically question for pertinent family history of clefting, parental consanguinity and age, pregnancy-related illnesses and infections, A total of 61,156 live births were reported during the 4.5-year study period. The number of children born with cleft lip and/or cleft palate, including submucous cleft varieties, totalled 117. The overall incidence for cleft lip and/or cleft palate in the cases reviewed was 1.91 per 1000 births (one per 523 births). The type and severity of cleft anomalies are presented in Table I. The incidence of clefts of the primary palate was noted to be 1.45 per 1000. The incidence of cleft lip alone was 0.80 per 1000, whereas that of cleft lip with cleft palate was 0.65 per 1000. Isolated cleft palate (including submucous cleft palate) was noted to occur in 0.46 per 1000 births. Gender distribution for the various cleft anomalies is pre- TABLE I Database on Cleft Forms Observed in the Study Population Clefts of the Primary Palate Cleft Lip Alone No. of cases 49 Incidence 0.80/1000 % of total cases 42 Classification of cleft as per the Smith modification of the Kernahan Y 1/0 ⫽ 3 12/0 ⫽ 5 1a/0 ⫽ 1 1b/0 ⫽ 1 1c/0 ⫽ 2 0/1⬘ ⫽ 5 0/1⬘2⬘ ⫽ 9 0/1⬘a⬘ ⫽ 1 0/1⬘b⬘ ⫽ 1 0/1⬘c⬘ ⫽ 2 1,2/1⬘c⬘ ⫽ 2 1,2/1⬘b⬘ ⫽ 1 1/1⬘2⬘ ⫽ 3 1/1⬘c⬘ ⫽ 1 1/1⬘b⬘ ⫽ 2 1c/1⬘2⬘ ⫽ 1 1b/1⬘2⬘ ⫽ 2 1a/1⬘2⬘ ⫽ 3 1c/1⬘ ⫽ 1 1b/1⬘ ⫽ 2 1a/1⬘ ⫽ 1 Clefts of the Secondary Palate Cleft Lip and Cleft Palate Cleft Palate Alone 40 0.65/1000 34 28 0.46/1000 24 00/1⬘6⬘ ⫽ 9 16/00 ⫽ 7 12/1⬘6⬘ ⫽ 7 16/1⬘6⬘ ⫽ 6 16/1⬘2⬘ ⫽ 3 1a/1⬘3⬘ ⫽ 3 1c/1⬘6⬘ ⫽ 2 16/1⬘c⬘ ⫽ 1 16/1⬘2⬘ ⫽ 1 1a/1⬘6⬘ ⫽ 1 6a/6⬘a⬘ ⫽ 3 6/6⬘ ⫽ 14 5,6/5⬘6⬘ ⫽ 7 4,5,6/4⬘5⬘6⬘ ⫽ 4 Vol. 113, No. 6 / 1551 EPIDEMIOLOGY OF CLEFT LIP AND PALATE TABLE II Sex Distribution for the Cleft Cases Observed Clefts of the 1⬘ Palate No. of cases Incidence % of total cases Boys Girls Clefts of the 2⬘ Palate Cleft Lip Alone Cleft Lip and Cleft Palate Cleft Palate Alone 49 0.80/1,000 42 29 20 40 0.65/1,000 34 24 16 28 0.46/1,000 24 13 15 sented in Table II. The left side was more commonly involved for both cleft lip and cleft lip with cleft palate, which was more often found in boys than in girls. Similarly, cases of bilateral cleft lip were also more commonly reported in boys. Conversely, there was a slight preponderance of girls represented in the cases of isolated cleft palate (Table II). More detailed data analysis was hindered in 11 cleft cases because of incomplete charts, the inability to confirm diagnoses and pertinent related information, and/or lack of adequate follow-up and survey information. These patients were excluded from further study. Data on the remaining 106 patients and their families with matched controls from similar villages, with comparable socioeconomic status, ethnic group, and number of children, constituted the basis for the remainder of the analyses. The frequency of associated malformations is presented in Table III. Syndromes are reported independently from nonsyndromic anomalies. A relatively higher incidence of consanguineous marriages was noted in the parents of children with cleft lip and/or cleft palate in comparison with matched controls (32 percent versus 18 percent). Consanguineous marriages are defined as first- or secondcousin marriages; marriages of more distant relatives were not considered consanguineous for this study. This figure achieved statistical significance (p ⬍ 0.05). First-cousin marriages were more commonly implicated than secondcousin marriages. A family history of cleft anomalies was present in 18 of 106 cases reviewed. The relationship of the cleft relative to the cleft child is reported in Table IV. Parental age data are reported in Table V. Both parents of the cleft children were found to be significantly older than matched controls. The mean number of siblings of the cleft children was 5.4 (range, one to 13) and 4.9 (range, one to 12) for controls. There was no statistical significance between groups. Childbirth- and pregnancy-related complications reported in the charts and obtained by interview and chart review are listed in Table VI. Approximately one-half of all mothers had received complete immunization schedules against the common infectious diseases in Pakistan, whereas 68 percent of mothers of cleft children denied appropriate interaction with a formally trained health care professional during the period of their pregnancy (Table VII). Only 32 percent of pregnant women received formal prenatal counseling, monthly physical examinations, and regular laboratory blood and urine testing during the entirety of the pregnancy. Nutritional and vitamin supplementation (including iron supplements) was given to 28 percent of the mothers of cleft children but was noted in 59 percent of the mothers of controls. A traditional Pakistani vilTABLE III Frequency of Associated Syndromic and Nonsyndromic Anomalies Seen in the Study Population No. Syndromic (10 patients) Pierre Robin sequence Hemifacial microsomia Down syndrome (trisomy 21) Edwards syndrome (trisomy 18) Van Der Woude syndrome Waardenburg’s syndrome Stickler syndrome Nonsyndromic (20 anomalies in 11 patients)* Hand/foot anomalies Ventricular septal defect Tetralogy of Fallot Pyloric stenosis Duodenal atresia Umbilical hernia Inguinal hernia Imperforate anus Hydrocephalus Facial asymmetry Coloboma Telecanthus Hypospadias Preauricular skin tags Microtia 3 2 1 1 1 1 1 3 1 2 1 1 1 1 1 2 1 1 1 2 1 1 * One patient had four anomalies, two patients had three anomalies, and two patients had two anomalies. 1552 PLASTIC AND RECONSTRUCTIVE SURGERY, TABLE IV Relationship of Cleft Relative to Cleft Child May 2004 TABLE VI Childbirth- and Pregnancy-Related Complications Seen in the Mothers of 106 Cleft Patients Relative No. Father Mother Sibling Maternal uncle/aunt Paternal uncle/aunt Maternal grandparent Paternal grandparent Cousin 6 5 7 2 1 1 2 3 * Five patients had more than one relative with an orofacial cleft. lage midwife (no formal health-related education) was involved in the care of the pregnant woman in over 98 percent of the cases. Complications No. Maternal infection Maternal fever Anemia Dietary deficiency Diarrhea Jaundice Bleeding Preterm birth Polyhydramnios Medication use Total 7 9 8 14 4 6 6 11 4 6 72 * Three mothers had five complications, six had four complications, two had three complications, and three mothers reported two complications over the course of their pregnancies that resulted in a child with a cleft. DISCUSSION Cleft lip and palate has been recognized as a major source of disability, preventing people from realizing their potential and contributing fully to society. In the developed world, many of these challenges have been redressed through the institution of a multidisciplinary approach to the child identified with an orofacial cleft.16 Rigorous attempts to maximize impaired speech, hearing, dental, nutritional, and intellectual functions have revolutionized contemporary cleft lip and cleft palate patient care. Surgical techniques have been refined such that a high level of aesthetic restoration is the rule rather than the exception.1 Unfortunately, in developing countries, access to rehabilitative and supportive treatment programs is limited or nonexistent. The early identification of infants born with cleft lip and palate is of paramount importance to allow timely intervention and to prevent the well-known sequelae associated with a lack of treatment. The complex, variable, and longterm problems that confront affected children are particularly disabling in these communities, where illiteracy demands an increased reliance on verbal communications. Furthermore, the lack of experienced craniofacial centers, resources, and services is compounded TABLE V Age of the Parents of Cleft Children versus Appropriately Matched Controls Parents of cleft children Parents of matched controls * Statistically significant (p ⬍ 0.05). Mother (yr) Father (yr) 27.3* 22.4 32.6* 27.1 by the relative scarcity of reliable epidemiologic data on the magnitude of the problem.17 The observed incidence of cleft lip and/or palate and isolated cleft palate in this study population was one per 523 live births. This figure places it between the rates attributed to adjacent populations in India (one per 781 live births) and Iran (one per 437 live births).7,16,18,19 The rates of clefting most closely parallel European rates, which range from one per 452 to one per 740 live births.20 Cleft lip alone was observed more often than combined cleft lip and cleft palate or isolated cleft palate (Table I). The left side was more commonly involved in the cleft lip–related anomalies (Table II). This observation has been found in other epidemiologic reviews of clefts but as yet does not have a clear explanation.3,6,9 –11 Similarly, boys predominated in the cleft lip and combined cleft lip with cleft palate groups (i.e., clefts of the primary palate), whereas there was a slight female trend in cases of isolated cleft palate (clefts of the secondary palate) (Table II). Although not following the classically described gender ratio of 2:1 (girls TABLE VII Health Care Access of Mothers of Cleft Children versus Appropriately Matched Controls to Immunizations, Prenatal Care, and Traditional Midwife Care* Immunization Monthly prenatal visits At least one prenatal visit Nutritional supplementation Traditional midwife care Mothers of Cleft Children Mothers of Controls 52 32 65 28 98 49 63 84 59 100 * Not formally trained in a health-related field. Vol. 113, No. 6 / EPIDEMIOLOGY OF CLEFT LIP AND PALATE to boys) for isolated cleft palate, the findings reflect trends seen in comparable epidemiologic reviews.9 –12,18 –20 The cleft classification of Kernahan,14 modified by Smith et al.,15 proved successful in describing the entire spectrum of cleft lip and/or cleft palate (primary palate) and isolated cleft palate (secondary palate) anomalies encountered in the study population (Fig. 1 and Table I). This system was easily teachable and accurate in conveying descriptive information. Data collection, tabulation, and digitization to a database were simplified, and verification of the cleft anomalies recorded by community health workers, nurses, house officers, registrars, and consultants was similarly performed with ease. This system of classification allows for a rapid cataloguing of the cleft anomaly with symbolic representations that readily communicate the type and severity of the cleft deformity in an easy-to-understand format (Table I). To the best of our knowledge, this is the only study where a cleft classification system was used to describe all cases in an epidemiologic study. The most commonly encountered presentation of isolated cleft lip was 00/1'2' (left cleft lip and alveolus). Cleft of the soft palate (06/ 0'6') was seen in 50 percent of the isolated cleft palate anomalies, whereas submucous clefts (06a/0'6'a') were observed in three patients. In the cleft lip with cleft palate group, complete left-sided cleft lip and palate (00/1'6') was the most frequent presentation observed. Bilateral and more severe cleft deformities were noted to occur more commonly in boys than in girls (Table II). The retrospective and prospective portions of the study were comparable in picking up cleft lip and combined cleft lip and cleft palate abnormalities. However, for the isolated cleft palate patients, a relatively greater number of cases were picked up in the prospective 6-month period in comparison with the retrospective 4-year period. For example, only one submucous cleft palate was noted retrospectively; however, two were picked up in the prospective wing of the study. This finding may be attributable, in part, to the fact that specific training was given to health care providers to search for a zona pellucida, bifidity of the uvula, notching of the posterior hard palate, and velopharyngeal incompetence manifesting as speech abnormality and/or feeding problems. The retrospective portion of the study likely underreported cases of submucous cleft 1553 palate and clefts of the secondary palate in general. The clefts of the primary palate, because of their more overt and anterior clinical expression, are more likely to be accurately represented. Only 21 of 106 patients (20 percent) manifested identifiable associated syndromic or nonsyndromic anomalies (Table III). Pierre Robin sequence was noted in three patients, all of whom presented with isolated cleft palate. One or more associated malformations were found in 11 of 96 nonsyndromal cleft cases (11 percent). The incidence of anomalies associated with cleft lip and cleft palate varies with different study populations and authors. In live births, Kumar et al.18 and Bonaiti et al.21 have reported figures approaching 30 percent, whereas others have reported figures of 13 percent and 19 percent, respectively, from African studies.22,23 The figures for syndromic and nonsyndromic anomalies are lower than what we expected because of high rates of consanguineous marriages. A comprehensive genetic or dysmorphology evaluation would have been ideal to assist in the ascertainment of all syndromes and anomalies, whatever their level of expression. This would have entailed considerable effort and time expenditure and is an element that will be planned in a subsequent site visit to Pakistan. Consanguineous marriages between first and second cousins are a fading yet acceptable part of Pakistani society. Similar marriage patterns are seen in the adjacent central Asian and Middle Eastern countries, and in predominantly Hindu India, in orthodox Jews, and in conservative Muslims. In the present study, consanguineous marriages in the parents of cleft children were noted to occur disproportionately in comparison with matched controls (32 percent versus 18 percent). Certainly, this is an important factor in the development of cleft anomalies and a host of other genetic abnormalities and should be discouraged. Interestingly, it seems that consanguineous marriages offered a form of security for a parent or child with a cleft. Marriage, procreation, and family life are central pillars of Pakistani society. This ensures that a suitable spouse is found for any individual of marriageable age, regardless of the presence or absence of a cleft, within or outside of extended families. A positive family history for an orofacial cleft was seen in 18 of 106 patients (17 percent), reinforcing the strong familial/genetic associ- 1554 ation seen in these conditions. All 18 of these children had a primary relative with a cleft, and five of these children had more than one relative with a cleft (Table IV). Some data in the literature have suggested that age over 30 years for both parents and advanced paternal age have been linked to the development of an orofacial cleft. The associations, however, are not well defined and could be confounding variables. For example, parents of cleft children are from lower socioeconomic backgrounds or, as this study has shown, may themselves may be afflicted with a cleft (Table IV). These factors may, in and of themselves, be explanations why one of these particular individuals may not be viewed favorably or as desirable by an eligible marital match, thereby delaying their age of marriage. In any event, increased parental age was noted in this study in the parents of cleft children. The mean maternal and paternal ages, 27.3 years and 32.6 years, respectively, were higher by approximately 5 years in comparison with matched controls (Table V). Pregnancy-related complications were noted in a large number of mothers of cleft children (Table VI). Many of the reported complications could be redressed with proper prenatal care, which was regularly available to only 32 percent of the mothers of cleft children. Dietary deficiency was seen in 14 mothers and was the most common problem encountered. Maternal infections, fevers, anemia, diarrhea, and untoward medication use (e.g., steroids, aspirin, anticonvulsants) are all potentially preventable and treatable conditions that may affect cleft development. Strengthening and expanding existing maternal health care initiatives and supplementary nutritional programs are key elements in this process. As the vast majority of women have contact with traditional midwives during the course of their pregnancies, these health care providers may be the best individuals to empower for delivery of this type of preventative care and health care education. A necessary prerequisite would include comprehensive educational programs for the midwives focused on maternal nutrition, vitamin supplementation, preventative health care (including regular blood pressure, urine, and physical examinations), and identification of maternal high-risk factors appropriate for referral to tertiary centers of care. Many forms of bias are inherent in a study of this nature. The orofacial clefting rate deter- PLASTIC AND RECONSTRUCTIVE SURGERY, May 2004 mined in this review of live births fails to take into consideration those neonates born outside the hospital system. As is true in many developing countries, the practice of home births is quite common in Pakistan and is a source of bias that must be accepted in a study of this nature. It is reported that 45 to 55 percent of births occur outside of formal hospitals in this particular region of Pakistan.13 It is reasonable to presume that these families are more isolated and would be more likely to have dietary deficiencies and other pregnancyrelated risk factors and to be of lower socioeconomic status; all of these factors adversely affect childbirths. Mortality rates among mothers and children would be presumed to be much higher in these groups because of newborn feeding difficulties, feeding with formula, water contamination, and undiagnosed congenital disabilities. Similarly, families that reside a considerable distance from the major towns of Pakistan tend to be more traditional and conservative and to have higher rates of consanguinity. All of these factors could have had an impact on the rates of clefting noted in this study. Neonatal deaths have also not been factored into the incidence rate. Furthermore, some studies have suggested that female infanticide skews cleft rates in the developing world, particularly for gender comparisons. Although this may be true for the other countries of south Asia, this practice is not seen in Pakistan because of its strict prohibition in Islam. Societal attitudes toward cleft individuals also seem to be influenced by the acceptance of the deformities as a manifestation of God’s will. As a result, many of the cleft patients and families interviewed did not appear to have guilt about their circumstance. Similar findings were noted by Kumar et al.18 in their review of clefts in Saudi Arabia. None of the children in the current study appeared to be overtly neglected, marginalized, or disadvantaged in their respective families or communities. Parents universally expressed their preference, if given the choice, of not having a child with a cleft or not to have been born with a cleft themselves, but the majority reported being comfortable with and accepting of their condition. This is reflected by the large number of parents who themselves are afflicted with cleft lip and/or cleft palate but who refuse to undergo any treatment. Resources, technical considerations, and financial constraints play a role in the decision Vol. 113, No. 6 / EPIDEMIOLOGY OF CLEFT LIP AND PALATE of a parent to defer treatment for their child or themselves. This is perhaps the most important consideration to address for developing countries and international aid groups. The Smile Train has recently become active in Pakistan, providing funding for local surgeons to perform cleft surgeries. The empowerment of capable, trained, and devoted physicians by the Smile Train will alleviate some of these concerns, making cleft repair and treatment a reality for many Pakistani children. CONCLUSIONS This study has provided population-based data on cleft lip and palate in a Pakistani study population and has added to the cumulative worldwide database on this entity. It is hoped that the information and results acquired from this survey will provide momentum in developing a regional cleft lip/palate database cataloguing the spectrum of cleft deformities present. To formulate any comprehensive plan to ultimately treat and manage these patients, epidemiologic studies are imperative to gauge the extent of the problem. Despite the limitations of this particular study, awareness that cleft lip and cleft palate in Pakistan is a significant clinical and developmental problem has been highlighted. Furthermore, a framework for data collection and review has been established with the ultimate goal of facilitating health-related policies that focus on resource use and cleft lip and palate prevention, care, and counseling. Future studies can be guided by this preliminary study focusing on specific environmental and genetic factors elucidated by this report. A preliminary, first study to evaluate the magnitude of cleft lip and palate in Pakistan was the goal of this work and was certainly overdue. Mohammed M. Elahi, M.D. 1600 Arch Street, Suite 508 Philadelphia, Pa. 19103 mmelahi93@hotmail.com ACKNOWLEDGMENT This study was supported by an educational grant from the Smile Train, New York, N.Y. REFERENCES 1. Jones, M. C. Facial clefting: Etiology and developmental pathogenesis—Advances in management of cleft lip and palate. Clin. Plast. Surg. 20: 671, 1993. 1555 2. Melnick, M. Cleft lip and cleft palate etiology: A search for solutions. Am. J. Hum. Genet. 42: 10, 1992. 3. Chung, C. S., Ching, G. H. S., and Morton, N. E. A genetic study of cleft lip and palate in Hawaii: II. Complex segregation analysis of genetic risks. Am. J. Hum. Genet. 26: 177, 1974. 4. Fraser, F. C. The multifactorial/threshold concept: Uses and misuses. Teratology 14: 267, 1976. 5. Hu, D. N., Li, J. H., and Chen, H. S. Genetics of cleft palate in China. Am. J. Hum. Genet. 34: 999, 1982. 6. Marazita, M. L., Melnick, M., Spence, M. A., and Hu, D. N. Family study of cleft lip and cleft palate in Shanghai, China. Am. J. Hum. Genet. 45: 243, 1989. 7. Nemana, L. J., Marazita, M. L., and Melnick, M. A genetic analysis of cleft lip with or without cleft palate in Madras, India. Am. J. Med. Genet. 42: 5, 1992. 8. Das, S. K., Runnels, R. S., Smith, J. C., and Cohly, H. H. P. Epidemiology of cleft lip and cleft palate in Mississippi. South. Med. J. 88: 437, 1995. 9. Chuangsuwanich, A., Aojanepong, C., Muangsombut, S., and Tongpiew, P. Epidemiology of cleft lip and palate in Thailand. Ann. Plast. Surg. 10: 7, 1998. 10. Ogle, O. E. Incidence of cleft lip and palate in a newborn Zairian sample. Cleft Palate Craniofac. J. 30: 250, 1993. 11. Srivastava, S., and Bang, R. L. Facial clefting in Kuwait and England: A comparative study. Br. J. Plast. Surg. 43: 457, 1990. 12. Murray, J. C., Daack-Hirsch, S., and Buetow, K. H. Clinical studies of cleft lip and palate in the Philippines. Cleft Palate Craniofac. J. 34: 7, 1997. 13. Canadian Foreign Service Institute. Pakistan: An Introduction. Hull, Quebec: Intercultural Learning, Canadian Foreign Service Institute, 1997. 14. Kernahan, D. A. On cleft lip and palate classification. Plast. Reconstr. Surg. 51: 578, 1973. 15. Smith, A. W., Khoo, A. K. M., and Jackson, I. T. A modification of the Kernahan “Y” classification in cleft lip and palate deformities. Plast. Reconstr. Surg. 102: 1842, 1998. 16. Ahuja, R. B. Primary definitive nasal correction in patients presenting for late unilateral cleft lip repair. Plast. Reconstr. Surg. 110: 17, 2002. 17. Elahi, M. M., Elahi, F., Elahi, A., and Elahi, S. B. Paediatric hearing loss in rural Pakistan. J. Otolaryngol. 27: 348, 1998. 18. Kumar, P., Hussain, M. T., Cardoso, O., Hawary, M. B., and Hassanain, J. Facial clefts in Saudi Arabia: An epidemiological analysis in 179 patients. Plast. Reconstr. Surg. 88: 955, 1991. 19. Taher, A. Y. Cleft lip and palate in Tehran. Cleft Palate Craniofac. J. 29: 15, 1992. 20. Derijcke, A., Eerens, A., and Carels, C. The incidence of oral clefts: A review. Br. J. Oral Maxillofac. Surg. 34: 488, 1996. 21. Bonaiti, C., Briard, M. L., Feingold, J., et al. An epidemiological and genetic study of facial clefting in France: I. Epidemiology and frequency in relatives. J. Med. Genet. 19: 8, 1982. 22. Orkar, K. S., Ugwu, B. T., and Momoh, J. T. Cleft lip and palate: The Jos experience. East Afr. Med. J. 79: 510, 2002. 23. Ademiluyi, S. A., Oyeneyin, J. O., and Sowemimo, G. O. Associated congenital abnormalities in Nigerian children with cleft lip and palate. West Afr. J. Med. 8: 135, 1989.