Richard S. Olney
Cynthia A. Moore
Cleft lip and cleft palate are important to public health in terms of birth prevalence, associated disabilities, costs of care, and psychosocial impact. Scientific studies relating to these issues are outlined in other chapters of this book. In this chapter, we focus on the practical application of scientific knowledge by public health providers to prevent and ameliorate birth defects at the community level. Some of the examples in this chapter do not necessarily apply directly to orofacial clefts. However, since these examples of birth defect programs include other malformations of similar public health importance such as neural tube defects, or are programs directed at exposures and outcomes that may also be related to orofacial clefts, they represent model approaches to public health aspects of birth defects that may also apply to cleft lip and cleft palate.
One public health program at the Centers for Disease Control and Prevention (Centers for Disease Control and Prevention, Division of Diabetes Translation, 2001) has defined its role in translating research findings into widespread clinical and public health practice in the following ways:
· Targeting special populations to improve access to affordable, high-quality services
· Supporting extramural prevention programs
· Researching better ways to apply scientific findings
· Strengthening surveillance systems to better define and monitor the burden of disease
This conceptual framework will be used here to discuss areas of public health policy and action that may apply to emerging epidemiologic, genetic, and clinical research findings related to cleft lip and cleft palate.
Improving Access to Affordable, High-Quality Services
The roles of providers and agencies in the public health aspects of genetic disorders and birth defects include preventing such conditions and developing and instituting measures to prevent suffering and related disabilities when such disorders occur (Khoury et al., 1993). Application of the latter approach, sometimes called tertiary prevention but more accurately known as disability prevention, is an important public health activity for children with orofacial clefts (Pope and Tarlov, 1991). In translating scientific advances into practice, public health agencies and providers become involved with clinical programs to ensure that affected children are identified and linked with specialty care shortly after birth, that the costs of such medical care are covered (often with public funds), and that appropriate interventions are actually provided. Public health agencies and related organizations have been involved with a variety of initiatives to ensure that these goals are addressed (Table 40.1).
As noted in Section II of this book, treatment of affected children has traditionally relied on multidisciplinary teams to address a variety of aspects of longterm care beyond surgical repair and often on cutting-edge advances in clinical practice that may be available only at referral centers in certain geographic areas. These teams have existed for many years (Ely, 1969; Ivy, 1971). However, active involvement of state public health agencies with craniofacial teams has been incomplete. Healthy People 2010 sets national public health priorities in the United States; in the chapter on oral health, objective 21-15 promotes efforts to increase the number of states that have a system for recording and referring children with orofacial clefts to craniofacial rehabilitative teams (US Department of Health and Human Services, 2000). As a baseline, 23 states surveyed and the District of Columbia had such systems in 1997 (US Department of Health and Human Services, 2000). Objective 21-16 advocates for craniofacial health surveillance systems, one purpose of which is to implement and evaluate interventions. In Britain, a craniofacial surveillance system (currently known as the Craniofacial Anomalies Register) has operated since 1982 (Hammond and Stassen, 1999).
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TABLE 40.1. Public Health Initiatives Relating to Comprehensive Clinical Care for Children with Orofacial Clefts and Other Special Healthcare Needs |
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Title V of the Social Security Act mandated comprehensive care by states for children with special needs, and state health departments have set up specific offices and coordinators for these efforts through funding by the federal Maternal and Child Health Bureau (currently part of the Health Resources and Services Administration, HRSA/MCHB) (Walker, 2000). Some of these state programs directly fund healthcare reimbursement for children with orofacial clefts who are seen in multidisciplinary craniofacial clinics. The HRSA/MCHB has also promulgated the National Agenda for Children with Special Health Needs to set specific goals (Table 40.1). Important outcomes of this initiative include adequate insurance coverage for all affected children and ongoing comprehensive care for all children. Another component of the agenda is early screening for special needs; e.g., the HRSA/MCHB (in partnership with the CDC and the federal Office of Special Education and Rehabilitation Services) now funds universal newborn hearing screening programs in many states, which should lead to interventions earlier in infancy for hearing impairment with or without craniofacial anomalies.
The medical home concept is closely related to comprehensive care initiatives for children with special healthcare needs. The essence of the medical home movement is to ensure continuous, coordinated, and comprehensive care for children with chronic conditions, which is a particular necessity when insurance coverage is provided in a managed care environment requiring a single provider to refer for multidisciplinary care (American Academy of Pediatrics Committee on Children with Disabilities, 1997). The HRSA/MCHB has also funded the American Academy of Pediatrics to establish the National Center of Medical Home Initiatives for Children with Special Needs. The goals of the center are to develop advocacy materials for medical home providers and issue recommendations that benefit children with chronic conditions and to assess outcomes (Table 40.1).
Prevention Programs
Examples of public health prevention programs for birth defects or other reproductive outcomes are listed in Table 40.2. State-sponsored prenatal screening programs, although better established than other prevention programs, primarily involve pregnancies affected with neural tube defects, abdominal wall defects, or multiple congenital anomaly syndromes such as trisomy 18 or 21 (Cunningham et al., 1998; Cunningham and Tompkinson, 1999; Kirby, 2000). These public health programs will not be considered in detail here because orofacial clefts are not common features of the currently targeted disorders and a limited number of public health agencies and providers are involved with the programs.
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TABLE 40.2. Birth Defect Prevention Programs |
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The folic acid story is an example of an evolving prevention program that could also potentially prevent orofacial clefts. The role of nutritional factors in preventing orofacial clefts is reviewed extensively in Section I of this book. In summary, some observational studies have shown risk reduction by folic acid/multivitamins in the occurrence of orofacial clefts, although more research is needed to fully evaluate this hypothesis. Based on strong epidemiologic evidence showing the efficacy of folic acid at reducing the risk for another group of congenital anomalies, neural tube defects, public health approaches to increasing folic acid consumption have proceeded in a variety of ways (Watkins, 1998). The most important interventions have included encouraging supplementation (consumption of multivitamins) and food fortification in the United States. These efforts have occurred through partnerships between such groups as federal and state public health agencies, professional organizations, community service and advocacy organizations such as the March of Dimes, and grass-roots spina bifida associations. Because some folic acid-related interventions will have general effects on public health and are not solely targeted to pregnancies at high risk for neural tube defects, these programs might lower the birth prevalence of orofacial clefts.
Smoking cessation programs are another example of widespread public health efforts aimed at effecting a variety of healthy outcomes that could also potentially lower rates of orofacial clefts, based on the epidemiologic evidence discussed elsewhere in this book. In the 1990s, studies showed that approximately one-quarter of U.S. women of reproductive age smoked, while reported smoking rates during pregnancy were slightly less than 20% (Centers for Disease Control and Prevention, 1994; National Center for Health Statistics, 2000). One of the Healthy People 2010 objectives (16-17) is to increase the cigarette abstinence rate among pregnant women to 99% (US Department of Health and Human Services, 2000). A meta-analysis of smoking cessation programs targeted specifically toward pregnant women showed them to be effective at reducing smoking rates as well as adverse outcomes clearly linked to perinatal tobacco use: low birth weight and preterm birth (Lumley et al., 2000).
A third type of prevention program is aimed at reducing exposure of pregnant women to teratogenic drugs. Currently known teratogens, such as anticonvulsant medications, have been associated with less than 5% of orofacial clefts (Abrishamchian et al., 1994). However, new gene-drug interactions may yet be identified (see Section I of this book), leading to prevention programs. Isotretinoin embryopathy is one condition that occasionally includes cleft palate in addition to other characteristic craniofacial defects, central nervous system abnormalities, and conotruncal heart defects (Fernhoff and Lammer, 1984). In 1988, the drug manufacturer (Hoffmann-La Roche, Inc., Nutley, New Jersey) together with the Food and Drug Administration (FDA) implemented a Pregnancy Prevention Program in women of childbearing age who were receiving isotretinoin (Mitchell et al., 1995). The pregnancy rate among women enrolled in this program was substantially lower than that in the general population, but this voluntary program enrolled only approximately half of the women taking the drug between 1989 and 1993. Even among the 177,216 women enrolled in the program, 402 pregnancies occurred. In 2000, an advisory committee to the FDA recommended that the isotretinoin program be further strengthened by making registration of female patients and verification of a negative pregnancy test mandatory (Food and Drug Administration, 2000; House Committee on Government Reform, 2000; Meadows, 2001). When the notorious teratogen thalidomide was approved by the FDA for limited use in 1998, the experience of the isotretinoin Pregnancy Prevention Program was considered by the FDA, CDC, and other public health providers in designing a program for its use (Lary et al., 1999). The System for Thalidomide Education and Prescribing Safety (STEPS) program was developed, which includes not only contraception and pregnancy testing but also mandatory registration of prescribers, pharmacies, and patients; informed consent forms for treatment; and tight controls over prescription and dispensation. Although the success of STEPS has yet to be measured, the designs of both of these pregnancy prevention programs can provide lessons for the use of other known teratogens associated with orofacial clefts such as anticonvulsants or when the use of “new” teratogens is considered in the future.
Application of Scientific Findings
Applying the results of birth defect-related genetic and epidemiologic discoveries to public health practice is a challenging prospect and has resulted in a spate of research to meet this challenge. Khoury et al. (2000) outlined a framework for this research, which includes four main components:
· Public health assessment
· Evaluation of genetic testing
· Development, implementation, and evaluation of population interventions
· Communication and information dissemination
Public health assessment includes application of surveillance and epidemiologic methods. This topic is discussed in Section I of this book. The second researchrelated component, evaluation of genetic testing, will become important as new molecular and/or biochemical risk factors for orofacial clefts are discovered. Guidelines for evaluation were promulgated by the Task Force on Genetic Testing (Holtzman and Shapiro, 1998; Holtzman and Watson, 1998). These guidelines include both initial evaluations and studies of the use of these tests in actual clinical and public health practice (postmarketing surveillance). The task force identified three important components in the assessment of genetic tests: analytic validity, clinical validity, and clinical utility. Analytic validity refers to the sensitivity, specificity, and predictive values of the test itself with respect to genotype. Clinical validity refers to these same parameters with respect to phenotype. Clinical utility measures the benefits of interventions that follow genetic testing.
Development, implementation, and evaluation of population interventions refer to the real-world application of basic scientific discoveries. Development of a new prevention program for orofacial clefts might involve principles similar to those that have been applied in neural tube defect prevention programs or novel approaches to behavioral or environmental modification of another type of risk factor. A good example of implementation of a genetic test is a pilot demonstration project of newborn screening for cystic fibrosis in the form of a statewide randomized trial in Wisconsin (Farrell et al., 1997, 2001). Evaluation of interventions refers to studies of their effect on morbidity or mortality; for birth defects, this would include the impact on birth prevalence after a prevention program is implemented. The latter would involve surveillance and birth defect monitoring, as discussed below. Evaluations of orofacial cleft morbidity prevention would involve the application of evidence-based medical care (see Section II of this book).
Communication and information dissemination are major components of birth defect prevention programs. Genetic counselors have developed an entire discipline for the study and practice of communicating information about specific genes involved with cleft lip and cleft palate or other disorders. Initial efforts to evaluate the training of genetic counselors, which occasionally takes place within schools of public health, were sponsored by the Office of Maternal and Child Health (now HRSA/MCHB) (Walker, 1998). Folic acid counseling is already the standard of care for genetic counseling about neural tube defect recurrence, and although prevention of orofacial clefts through multivitamin use needs further study, discussions about vitamins may also be important in genetic counseling about recurrence risks for families of children with orofacial clefts (Harper, 1998; Itikala et al., 2001). Prevention programs involved with modifying environmental risk factors, such as smoking or folic acid intake, rely primarily on changing knowledge, attitudes, and behavior of women of childbearing age. For this reason, public health agencies involved with birth defect prevention have increasingly relied on behavioral scientists and researchers in health communication to develop effective prevention messages. Sometimes this has involved the use of novel techniques, such as analysis of survey databases to identify a target audience, selection of focus groups to define motivational concepts, and testing of these concepts in a controlled setting (Centers for Disease Control and Prevention, 1998; Daniel, 1999).
Surveillance and Monitoring Systems
Section I of this book includes a discussion of epidemiologic issues in birth defect surveillance. Table 40.3 illustrates some uses of birth defect surveillance systems for public health action and policy. Many birth defect surveillance systems have been established in response to concerns about identifying and controlling teratogens, although methodologic issues have put identification of new teratogens lower on their program agendas (Khoury and Holtzman, 1987). Nevertheless, clusters of birth defects and public concerns about specific environmental exposures frequently surface. Occasionally, high rates of orofacial clefts in specific places and times have prompted investigations. For example, a high orofacial cleft rate of 7/1000 births in the Netherlands in the 1960s led to a study that implicated, but could not prove, local chemical combustion as a risk factor (ten Tusscher et al., 2000). An East German secular trend study showed that local rates of orofacial clefts increased after the Chernobyl reactor accident in 1986, but this type of study also can only suggest and not prove causality for etiologic factors (Zieglowski and Hemprich, 1999).
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TABLE 40.3. Examples of Uses of Birth Defect Surveillance for Public Health Action and Policy |
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Registry-based studies can help to quantify risks when clusters have suggested etiologies for certain birth defects, which can ultimately lead to policy recommendations. In the early 1990s a prenatal diagnostic procedure, chorionic villus sampling, was associated with a transverse terminal limb deficiencies based on cluster reports, but early recommendations developed at the National Institutes of Health suggested counseling only about a “possible” risk (Report of National Institute of Child Health and Human Development Workshop on Chorionic Villus Sampling and Limb and Other Defects, 1993). A multistate, registry-based casecontrol study subsequently showed that an increased risk for limb deficiency after the procedure was statistically significant, but lower than first suggested by the early cluster reports (Centers for Disease Control and Prevention, 1995). The results of this study led to new recommendations by the CDC for counseling that (for the first time) quantified the risk; the CDC risk figures were subsequently adopted in part by a policy-making committee of the American College of Obstetricians and Gynecologists (American College of Obstetricians and Gynecologists Committee on Genetics, 1996).
Surveillance also has the potential to improve medical care for children with orofacial clefts. One of the uses of birth defect surveillance systems is early identification of children who are eligible for social services and special programs (Lynberg and Edmonds, 1994). In some states and countries, birth defect registries are linked to, or part of, a larger system of early identification and case management for children with special healthcare needs. In a 1999 directory of birth defect surveillance programs, 13 U.S. states listed “service delivery” as one of the uses of their data (Centers for Disease Control and Prevention, 2000; Montgomery and Miller, 2001). In a 1996-1997 survey, eight states responded that they linked their birth defect surveillance systems to their databases of children with special healthcare needs (Kirby, 2000). The challenge for the future of database integration is to increase the number of states performing such activities and to demonstrate to the lawmakers and agencies responsible for funding that they contribute to better outcomes (Walker, 2000).
Finally, birth defect monitoring is important to assess the effects of prevention programs. For example, efforts are under way to judge the effect of folic acid prevention programs on secular trends in neural tube defect rates (Rosano et al., 1999). A similar examination of trends in orofacial cleft rates could also provide epidemiologic evidence about the contribution of folic acid fortification to orofacial cleft prevention (Itikala et al., 2001). Neural tube defect trend studies are confounded by prenatal diagnosis. In studies of birth prevalence rates of clefts over time, as mentioned in Chapter 11 of this book, similar confounding is less likely to occur, even with increasing sophistication of prenatal ultrasound, such as the use of three-dimensional techniques. Anticipating the need for these studies is important for placing methodologically sound surveillance systems that include orofacial clefts in as many geographic areas as possible.
Concluding Remarks
Last (2001) defined public health as a combination of social institutions, practices, and scientific disciplines, the aim of which is to improve community health through collective action. Practical efforts to translate scientific advances related to orofacial clefts into improved community outcomes must proceed on several fronts. These efforts often start with legislative or policymaking initiatives; work through innovative, scientifically based prevention or treatment programs; and end with surveillance and monitoring to evaluate their success or failure. In other areas of maternal and child health, medical therapy and public health practice have had dramatic effects, such as 10-fold to 100-fold decreases in infant and maternal mortality over the last century (Wilcox and Marks, 1994). A prevention achievement of this magnitude for cleft lip and cleft palate would be a more complicated but equally worthy goal.
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