BASIC REPRODUCTIVE CARE

Basic reproductive care, which includes family planning, and preconceptional, prenatal, and neonatal care, is the foundation for improving neonatal and infant mortality and reducing birth defects. As infant mortality rates fall, birth rates tend to decline because parents become increasingly confident that the children they conceive will survive childhood. This trend is strongest where family planning is accessible and effective.

LOW-COST PREVENTIVE STRATEGIES

These low-cost interventions to prevent birth defects have been found to be affordable in even the poorest settings. They address some important risk factors and involve family planning, public health campaigns, fortification of staple foods, maternal and child health, and infectious disease control.

Folic Acid Fortification

The predominant cause of NTDs is folate deficiency in the early weeks of pregnancy (Oakley, 1993). Randomized controlled trials in Europe showed that folic acid supplementation in early pregnancy reduced NTDs by 70 percent (MRC Vitamin Study Research Group, 1991) and 100 percent (Czeizel and Dudas, 1992). A randomized controlled trial from India was halted because of the ethical need to provide folic acid to all participants once its effectiveness had been established. The findings of that study supported the conclusion that folic acid deficiency is the predominant cause of NTDs (Indian Council of Medical Research, 2000). In a large, nonrandomized community intervention study in a high-prevalence area (4 to 5 NTDs per 1,000 births) of China, pregnant women received daily supplements of 400 micrograms of synthetic folic acid before and during the first 28 days of pregnancy. This prevented 85 percent of NTDs among pregnant women taking folic acid more than 80 percent of the time (Berry et al., 1999) (see Box 3-1).

BOX 3-1

Preventing Neural Tube Defects with Folic Acid Supplementation in China. From 1993 to 1996, a large population-based observational study tested the ability of periconceptional folic acid supplementation to prevent neural tube defects (NTDs) in infants. (more...)

Although folic acid is present in leafy vegetables, legumes, and citrus fruits, it is unlikely that dietary advice alone can adequately increase consumption of these foods by those at risk. The above studies led the United States to fortify cereal grains with synthetic folic acid to increase consumption of the nutrient by an average of 100 micrograms a day (Food and Drug Administration, 1996). Although this amount represents just one-quarter of the daily consumption recommended, it raised blood folate to levels that decreased NTDs by about 20 percent (Green, 2002; Oakley 2002a). The United Kingdom and Chile fortify at about twice the U.S. level. Since Chileans consume twice as much wheat as each of the other populations, the average woman in Chile is estimated to receive the recommended level of 400 micrograms of synthetic folic acid daily (Oakley, 2002a). Folic acid fortification is being introduced in several South and Central American countries, many of which already fortify wheat flour with other B vitamins. Folic acid is so inexpensive that the cost of the vitamin premixture hardly changes with its addition. In countries where folic acid fortification is not already under way, its cost is estimated at 0.1 percent of the total cost of flour.

Fortification overcomes the logistical problems of supplementation in early pregnancy as well as taking a complete regimen. However, almost universal coverage for women of reproductive age is relatively inexpensive. Fortification is recommended at a level of 240 micrograms per 100 grams of a widely consumed staple food (Oakley, 2002b). Supplementation is useful where fortification is not possible or is below the recommended level (Committee on Medical Aspects of Food and Nutrition Policy, 2000).

Recommendation 3. All women of reproductive age should routinely receive 400 micrograms of synthetic folic acid per day for the reduction of neural tube defects. This is best accomplished through fortification of widely consumed staple foods. Where fortification is not feasible or is incomplete, daily supplementation programs should be provided for women before and during pregnancy.

Universal Salt Iodization

The primary cause of iodine deficiency disorders (IDDs) is insufficient iodine in the diet. The adult requirement for iodine can be met with 100 to 150 micrograms daily, and an additional 50 micrograms daily during pregnancy (Stanbury, 1998; World Health Organization, 2001). Correction of maternal iodine deficiency before conception is necessary to avoid adverse effects on the fetus. Measurement of urinary iodine is a convenient and reliable method for assessing iodine nutritional status in a community. This method is more accepted and considerably less expensive than the use of thyroid-stimulating hormone or other thyroid hormone measurements (Dunn et al., 1994; World Health Organization, 2001).

Iodine deficiency may be exacerbated by goitrogens, which interfere with the incorporation of iodine into thyroxine (Geelhoed, 1999). The effects of goitrogens can be mitigated by ensuring a more-than-adequate intake of iodine; avoiding consumption of thiocyanate-containing vegetable products such as cassava; and cooking potentially goitrogenic foods to reduce the goitrogen content (Bourdoux et al., 1982). Soaking foods is also effective in reducing the goitrogen level, but vitamin A and other nutrients are also lost in this process. Vitamin A deficiency can be addressed with dietary supplements (Vanderpas et al., 1993).

Iodine, a volatile trace element, is more abundant in the sea than on land. Except in certain geological regions (Li et al., 1989), iodine has been largely depleted from world soils (McClendon, 1939). Plants do not require iodine for healthy growth, and the amount of iodine in plants and animals generally reflects the low levels in soil. Thus to prevent iodine deficiency, most populations need supplementation (Hetzel and Maberly, 1986).

The accepted strategy for eliminating iodine deficiency is universal salt iodization (Stanbury, 1998), which is among the most cost-effective health interventions (World Bank, 1993). However, since this estimate does not encompass an assessment of the full impact of IDDs, the actual cost is likely to be lower (World Health Organization, United Nations Children's Fund, International Council for the Control of Iodine Deficiency Disorders, 1999). The customary level of fortification is 25–50 milligrams of iodine per kilogram of salt (World Health Organization, 1996b). The fortified salt product costs only slightly more ($0.02–$0.06 per person annually) than the unfortified product.

In populations with endemic cretinism and IDDs, iodized oil has been administered to entire populations as an emergency prophylactic and therapeutic (Delange, 1996; Geelhoed, 1999). In a Central African population in remote Congo, for example, an intramuscular injection of iodized oil was found to control goiter and cretinism and protect iodine stores for a period of 1 to 5 years, which reduces concerns about compliance (Geelhoed, 1999). Iodization of drinking water and bread has also been shown to provide a safe and cost-effective alternative in some settings (Elnager et al., 1997).

National leaders at the 1990 World Summit for Children set the goal of virtually eliminating this deficiency by the year 2000. In 1990, less than 20 percent of household salt was iodized, and more than one-third of the world's population was recognized as having inadequate dietary iodine. By 2002, more than 70 percent of household salt worldwide was iodized. Annually, this supplementation protects about 85 million infants, but another 35 million infants remain unprotected (Ramalingaswami, 2000). Figure 3-1 shows the percentage of households worldwide that use iodized salt, and efforts are under way to reach those households by 2005.

FIGURE 3-1

Distribution of households by their use of iodized salt. SOURCE: United Nations Children's Fund, 2000a.

The rapid progress of the last decade has demonstrated the effectiveness of national “ownership” of the challenge (Ramalingaswami, 2000) and close collaboration among public, private, civic, and scientific groups to support the production of good-quality iodized salt, the delivery of only iodized salt, persistent market outreach to all parts of the country, periodic advocacy to sustain political commitment, and continued education to sustain public demand.

Recommendation 4. A program of universal fortification of salt with 25–50 milligrams of iodine per kilogram of salt used for human and animal consumption should be adopted to prevent iodine deficiency disorders.

Immunization Against Rubella

Rubella infections are common worldwide and are strongly teratogenic. Vaccination programs in several, mostly developed, countries prevent virtually all cases of congenital rubella. Some countries have immunized all young children, some have immunized prepubescent females, and some have used a combined approach—with measles-mumps-rubella (MMR) vaccine (Immunization Working Group, 2000; Massad et al., 1995). By 1996, 78 countries worldwide reported national rubella vaccination programs. Included among these were 43 percent of Latin American, 12 percent of Eastern Mediterranean, 5 percent of South East Asian, and 11 percent of the Western Pacific populations. Notably absent were African countries (Robertson et al., 1997).

The decision to introduce rubella vaccination into a country or region should be based on the susceptibility of women of childbearing age, the burden of disease due to congenital rubella syndrome (CRS), the strength of the measles immunization program, the infrastructure and resources for immunization, the record of injection safety, and other priority uses for limited health resources (World Health Organization, 2000b). In countries where more than 80 percent of the population is immunized for other childhood diseases, rubella should be included in the immunization program. In countries where immunization coverage is lower than 80 percent, overall coverage should be increased before introducing rubella immunization because vaccination can interrupt natural transmission during childhood and actually increase the number of women who are not immune (Banatvala, 1998). A vaccination strategy developed and implemented in Brazil was able to eliminate CRS in 2 years (see Box 3-2).

BOX 3-2

Rubella Vaccination in São Paulo, Brazil. Using a model based on epidemiological and cost-effectiveness data, public health officials in São Paulo, Brazil, developed and implemented a strategy for rubella vaccination in 1992. Children (more...)

The most rapid reduction in CRS has been achieved with mass campaigns for all women of childbearing age. Checking for rubella antibodies before conception allows those who test negative to be immunized and those who test positive to be reassured. The benefits are considerable, while the main risk is the inappropriate reassurance of women who have false-positive tests (Tookey et al., 1991). All evidence indicates that rubella virus vaccine does not pose a risk to the fetus, so prior screening for pregnancy is unnecessary (Josefson, 2001; World Health Organization, 2000b). Vaccination of women of childbearing age against rubella has been shown to have a benefit-to-cost ratio of 11 to 1 in the United States (Hatziandreu et al., 1994) and a benefit-to-cost ratio of more than 1 in several developing-country studies (Hinman et al., 2002).

Eradication of rubella is feasible because it infects only humans and the vaccine is highly immunogenic, highly protective, affordable in all but the poorest countries, and can be administered in conjunction with measles and rubella vaccines and as part of a standard immunization schedule at 9 months of age (Plotkin et al., 1999). Eradicating rubella has not, however, been recognized as a priority in low-income countries (Banatvala, 1998). Combining rubella and measles vaccines can significantly reduce the cost of rubella immunization (Cutts and Vynnycky, 1999). In Latin America and the Caribbean, for example, 20,000 or more infants are born with CRS each year, yet a one-time mass immunization of all females aged 5 to 39 years could control both rubella and CRS (Hinman et al., 1998).

Surveillance of rubella and CRS following an eradication campaigns can be a challenge as rubella is often unreported and sometimes asymptomatic. Rubella epidemics are monitored using immunoglobulin M (IgM) testing in serum and saliva samples (Perry et al., 1993). Simple hearing tests for infants would improve case ascertainment (Plotkin et al, 1999), while testing all infants with microcephaly, developmental delay, hearing loss, microphthalmia, congenital cataracts, and congenital heart disease would capture a more complete estimate of CRS incidence.

Recommendation 5. Women should be vaccinated against rubella before they reach reproductive age to prevent congenital rubella syndrome.

PROVISION OF IMPROVED CARE

The health care provided to children and adults with birth defects should always be comparable with the care provided for other medical conditions and the best possible for the resources available. In many settings this may be very basic, but even where health care resources are limited, affordable and effective options exist for the treatment and rehabilitation of those with birth defects. Early diagnosis—prenatal or neonatal—provides the best chance for effective treatment. Counseling of parents should also address future pregnancies and how the risk for a future pregnancy to involve a birth defect can be lowered.

Treatment

An important aspect of reducing the impact of birth defects is access to treatment. Although some disorders cannot be treated cost-effectively or at all, others can be corrected partially or entirely by therapies that are clinically- and cost-effective. Treatments can be made available by screening for patients with treatable conditions, then referring them to secondary and tertiary centers. These opportunities are frequently overlooked by policy makers and health professionals in developing countries, and access to treatment in many countries is limited (Christianson, 2000; World Health Organization, 1999).

Prenatal or early neonatal diagnosis can be important for scheduling surgery or initiating therapy before conditions become more severe or irreversible. While few tertiary centers in low-income countries can undertake complex surgery such as cardiac procedures for children with congenital heart disease, simpler surgical procedures are generally available but with limited access. The setting of priorities for the development of surgical capacity should be based on the resources required, current health care capacity, the availability and sustainability of technical expertise, and cost-effectiveness in comparison with other health care services.

Each country must establish clear priorities for the provision of treatments based on the cost-effectiveness of specific therapies and surgeries as compared with other health care services. This process is complicated by the lack of evidence on the cost-effectiveness of many services, including neonatal surgery, even in developed countries (Stolk et al., 2000). Long-term follow-up to estimate the lasting success of surgery and other therapies is complicated by the difficulty of identifying an outcome that is comparable for different surgeries and treatments. Moreover, generic quality-of-life measurements used for adults have to be adjusted to reflect children's understanding and perception. The following discussion presents therapies that are employed successfully in many developing countries.

Talipes or clubfoot

Infants with talipes include those whose deformity can be resolved through manipulation and passive stretching, and those who require surgery (Porter, 1987). In either case, early intervention is critical to correcting the condition and obtaining a foot that is supple, painless, plantigrade, and of normal shape and function. Serial manipulation, a gentle and gradual method of elongating the contracted tissues, should begin within a day or two of birth (Sinha, 1987; Alexander et al., 1999). By 12 weeks of age, the soft tissues of the infant foot are far less pliable, so only surgery can correct the condition (Sinha, 1987). For this reason, talipes can be considered an orthopedic emergency (Scott and Evans, 1997).

The principles of surgical treatment for talipes have been recognized for nearly 150 years: surgery should be early; it should correct the deformity; and the correction should be maintained—at first with a cast and later with a splint or brace worn at night (Porter, 1987). The surgical techniques employed depend on the severity of the condition, the age of the patient, and the health care setting (Alexander et al., 1999; Porter, 1987; Jellis, 1988). Early surgery may be appropriate for a child whose family is unlikely or unable to comply with routines for manipulation of the foot; however, the risk of injury during complex procedures increases significantly for very small feet (Turco, 1974). When manipulation fails, bone surgery can make the foot plantigrade, but this generally compromises mobility (Porter, 1987).

Most of the treatment of talipes in Africa is provided by medical officers without specialized training. In East Africa, for example, only 10 percent of children with talipes are likely to reach a specialist because of poor communications, travel expenses, and parental reluctance to leave family and crops. Patients who do reach surgeons often face delays in treatment due to the inadequate health care resources (Jellis, 1988). Efforts to overcome these challenges have met with variable success. A weekly “clubfoot clinic” established in a teaching hospital in Lusaka, Zambia, corrected 287 feet, 133 of them surgically over a 4-year period, with only eight relapses (Parekh, 1985). In this study, 95 percent of the patients attended the clinic regularly during treatment, and most returned for checkups even after full correction. In contrast, a program offered by a nonspecialist medical officer at a 78-bed rural mission hospital in Tanzania was considered unsuccessful because of poor parental compliance (Scott and Evans, 1997). Despite improvement in all cases, none of the 26 children attended over a sufficient period of time to be cured or referred for surgery. Other authors have also described low-cost, locally appropriate technologies for treating talipes (Sengupta, 1987; Eyre-Brook, 1986; Hadidi, 1974). Box 3-3 describes simple surgical techniques developed in Calcutta to correct talipes.

BOX 3-3

Managing Talipes in India. In the course of 20 years, beginning in 1964, 5,312 patients with talipes were treated with a success rate of 85 percent at Calcutta's Institute of Child Health and Postgraduate Education. The hospital, an advanced center for (more...)

Parental education on the etiology and treatment of talipes is key to overcoming major barriers to compliance: successful treatments are available; surgery may be required; and after correction, periodic checkups should continue until the child's growth is complete. Families of infants undergoing manipulative treatment of the foot need to understand the importance of regular cast changing and manipulation, as well as how to care for the cast and perform neurovascular checks on the immobilized foot (Alexander et al., 1999). They should be encouraged to promote normal growth and development, including sitting up and crawling, while the foot is immobilized (Kryzer, 1991; Alexander et al., 1999). Postcorrection follow-up for talipes could be incorporated into local community-based rehabilitation or maternal and child health programs (Scott and Evans, 1997).

Cleft lip and/or cleft palate

Early establishment of feeding is a priority for neonates with cleft lip and/or cleft palate. Prenatal detection of the condition, available in some urban areas, can help parents to prepare for feeding and other special care of their child (Bender, 2000). Surgical repair of the lip can be done at 3 months and palatal repair at 6 months of age. This surgery, which is simple and effective, is available in several developing-country settings through the services of visiting surgeons supported by international foundations such as Operation Smile (see Box 3-4) and Medical Group Mission Christian Medical and Dental Society (Smith et al., 1991).

BOX 3-4

Surgical Correction of Cleft Lip and/or Palate. The impact of this birth defect can be significantly decreased by a simple plastic surgery procedure that costs approximately $750, takes as little as 45 minutes, and can be performed in hospitals and clinics (more...)

As children with cleft lip and/or cleft palate grow, their condition can cause a variety of physical, functional, and social problems. These can be minimized when treatment is available and when families, teachers, and the community are informed about the cause and difficulties associated with the condition. Support and education are key components of ongoing care (Chapados, 2000). Comprehensive treatment, which is not accessible for most developing country populations, can include speech and language therapy, preventive and restorative dental care, orthodontics, secondary surgery, otolaryngology for hearing problems, and psychological counseling (Cockell and Lees, 2000).

Isolated cases of cleft lip and palate show strong familial aggregation with a significant genetic component (Christenson and Mitchell, 1996). The risk of recurrence is, however, generally low. Surgical repair is generally effective (Czeizel and Hirschberg, 1997) and the isolated defect is not an indication for pregnancy termination (Czeizel and Hirschberg, 1997), but orofacial defects may be associated with congenital malformations of the limbs, spine, and cardiovascular system (Pilu et al., 1986). Fetal karyotyping can detect associated chromosomal anomalies or syndromes (Bender, 2000; Cockell and Lees, 2001).

Congenital heart disease (CHD)

In developed countries, CHD is diagnosed by ultrasound and repaired during infancy, but most developing countries lack the infrastructure necessary to treat this condition. Researchers estimate that hundreds of thousands of children are born each year with surgically treatable CHD. Most are not treated and die as children or teenagers (Cartmill et al., 1966; Rygg et al. 1971; Kirklin and Barrat-Boyes, 1993). However, hundreds of these children have been assisted without charge in developed countries or by traveling surgical teams supported by charitable organizations. One such organization, the Save a Child's Heart Foundation, has also assisted some institutions in developing countries in the establishment of CHD treatment capabilities (see Box 3-5) (Cohen et al., 2001).

BOX 3-5

Treatment of Congenital Heart Disease. Many developing-country children die of simple congenital heart lesions that can be repaired with a high success rate and at relatively low cost. To expand the availability of cardiac care to such children, the Israel-based (more...)

Developmental dysplasia of the hip (DDH)

Early diagnosis of DDH and simple, noninvasive postural treatments can prevent a severe and crippling condition. Without these early treatments, true dislocation of the hip requires a series of complicated surgeries and rehabilitations, the results of which are frequently unsatisfactory. The most widely used diagnostic screen for DDH, the manual Ortolani-Barlow (O-B) test, is often included in a routine neonatal clinical examination in developed countries (Leck, 2000). Its usefulness depends on the skill and experience of the pediatrician, physical therapist, or orthopedic surgeon in identifying unstable hips, particularly those most likely to degenerate into full dislocation (Medbø, 1961; Leck, 2000). Ultrasound provides a similar detection rate but may have a higher false-positive rate in primary DDH screening.

Clinical examinations in industrialized countries have been shown to detect approximately three-quarters of neonates whose hips are or will become dislocated. If the identified neonates are treated promptly by splinting, about two-thirds will not develop DDH (Leck, 2000). This estimate is, however, complicated by high levels of false-negative and false-positive results. Fewer false positives are likely if the O-B test is conducted at 6 weeks of age because many hips that appear dysplastic at birth stabilize without treatment by that time. Treatment appears to be equally effective at 6 weeks and can be undertaken successfully in children up to 2 years old (Kim et al., 1990), often through noninvasive methods (Ramsey et al., 1976; Mendes and Roffman, 1980; Kim et al., 1990). Early treatment maintains the thighs in a flexed and partly abducted position so that the head of each femur remains deep within the acetabulum, encouraging it to encompass the femoral head more completely. To maintain this position, the thighs are splinted for weeks to months (up to a year). Two widely used methods are the Pavlik harness, which holds the legs in soft stirrups, and the von Rosen splint, a solid support. These splinting methods have not been compared through randomized trials, nor have they been developed for optimal performance (Leck, 2000). Either splint can cause ischemic or avascular necrosis of the femoral head, which is often accompanied by reduced femoral growth. This effect can be minimized by maintaining the hips in moderate, rather than extreme, abduction (Leck, 2000). Dislocated hips that fail to respond to early splinting and those detected and treated in older children can be managed with a range of surgical procedures, depending on the child's age and the degree of dislocation (Kim et al., 1990).

Oculocutaneous albinism

For affected children, the symptoms of the disorder can be treated, and health education can improve the home care (and, eventually, self-care) of affected children and dispel misconceptions that surround the condition.

Affected children are extremely sensitive to the sun and have poor vision. Sun protection is critical since those affected can be severely sunburned from minute-long exposures, which over time make them vulnerable to skin cancer. Covering the skin with long-sleeved shirts, long pants, and wide-brimmed hats helps protect from exposure to ultraviolet A (UVA) radiation. Sunscreens with a sun protection factor (SPF) rating of greater than 25 should be used at all times (King et al., 1996). Vision problems, such as hyperopia, myopia, and astigmatism, require correction to obtain the best possible visual acuity (King et al., 1996). Nearly every respondent among 138 school children with albinism in rural Zimbabwe reported problems in school due to poor vision (Lund, 2001). Yet most of these children can function in a regular classroom, provided the teacher and school attend to their special vision needs (King et al., 1996).

Adults with albinism frequently encounter social problems associated with their appearance, including difficulty in finding employment (Lund, 1998). A survey of attitudes toward people with albinism conducted in urban Soweto, South Africa, found that although they may be accepted in their community, people with albinism were regarded as abnormal and perhaps not fully human (Kromberg, 1992). Negative attitudes persist and are based on myths and superstitions concerning albinism, the most pervasive being that people with the condition do not die normally, but “vanish.” Treatment of the condition and education of the public about the medical cause should be used to dispel this and other myths, and allow affected individuals to be accepted (and to accept themselves).

Recommendation 10. Children and adults with birth defects should receive the best medical care that is available in their setting, including, where possible, medication and surgery. Treatment should be undertaken as early as possible and be provided through an organized referral process.

Rehabilitation

Many infants with severe birth defects experience lifelong disability requiring long-term treatment or rehabilitation (Carey, 1992; World Health Organization, 1996a, 1999b). There are promising models of rehabilitation services for children with birth defects even in settings where professional resources are extremely limited. These models are based in communities: schools, hospitals and other institutions, and primary health care. The more comprehensive models are in the primary care system and are based on a national rehabilitation strategy. Although this report focuses on the care of infants and children with birth defects, it is important to recognize that rehabilitation programs are also needed for adults impaired by lifelong conditions. In many cases, appropriate education and rehabilitation for children and adults substantially increases their ability to function independently and contribute to family and community responsibilities.

Community-based rehabilitation (CBR)

CBR has been defined as a strategy in communities for the rehabilitation, equalization of opportunities, and social integration of people with disabilities (International Labor Organization, United Nations Educational, Scientific and Cultural Organization, and World Health Organization, 1994; United Nations Children's Fund and the Ministry of Education and Science, Spain, 1994). The strategy mobilizes local resources and enables people with disabilities and their communities to create their own solutions and programs for rehabilitation. It also addresses the isolation and stigmatization experienced by people with disabilities and encourages those with disabilities to live lives that are as normal as possible and are integrated into society. Disabled children are encouraged, where possible, to attend public schools with the goal of their not being limited by different social expectations or environmental constraints (Groce, 1999). The Jamaican program described in Box 3-6, is an example of how individuals with disabilities can be viewed as partners in national development.

BOX 3-6

Community-Based Rehabilitation in Jamaica. Jamaica's first community-based rehabilitation program, 3D Projects (“Dedicated to the Development of the Disabled”), began in 1985. At that time, few services for people with disabilities existed (more...)

Since 1983, WHO has produced training manuals for CBR workers and promoted CBR as the most appropriate model of rehabilitation for people with disabilities, including those due to birth defects (World Health Organization, 1980, 1993; Helander et al., 1989). While the WHO approach to CBR is largely home-based, model center-based approaches have also been developed (Werner, 1987).

The advantages of the CBR approach are its accessibility to low-income families and its ability to work with low-cost, locally available resources. The disadvantages are the lack of skilled resources, funds, and volunteered time; the difficulty of monitoring the quality of services and effectiveness in reaching the desired outcomes; and the inadequate opportunities for ongoing training and advancement of rehabilitation workers. Even with these drawbacks, CBR may be the most viable and cost-effective model for rehabilitative care in developing countries provided interventions are flexible, sensitive to cultural beliefs, appropriate to the country's current level of development, and compatible with local resources and development priorities.

School-based models

Educational opportunities for children with disabilities are limited in low-income countries. When available, they range from highly segregated, specialized residential and day schools to special classes in regular schools to a fully mainstreamed or inclusive education. Little information is available on the extent to which mainstreaming is practiced in low-income countries. Promotion of this approach began internationally following such agreements as the United Nations Educational, Scientific and Cultural Organization (UNESCO) Declaration of Education for All, which stipulates that all countries have a responsibility to provide equal access to education for children with disabilities as an integral part of the education system (Haddad, 1990; UNESCO and Ministry of Education and Science, Spain 1994). CBR and inclusive education appear to be mutually reinforcing, since CBR programs attempt to place children in regular schools, and teachers derive support from CBR workers when they accept children with disabilities (Thorburn, 2000). Box 3-7 describes school-based programs and other activities of the Bangladesh Protibondhi Foundation.

BOX 3-7

Rehabilitation Activities at Bangladesh Protibondhi Foundation. The Bangladesh Protibondhi Foundation (BPF), established in 1985, provides services and undertakes research for disabled children in Bangladesh. Key activities and achievements include: (more...)

Reports from some low-income countries indicate that many schools do not have the facilities, trained teachers, or positive attitudes required to accommodate children with disabilities (Mariga and Phachaka, 1993). Given the already overcrowded environment of government schools in most low-income countries, a major commitment of resources is required to accommodate these children.

Institution- and hospital-based models

Institutional care and hospital-based services for children with birth defects are present in many low-income countries but serve only a small fraction of the children who need them. Rehabilitation specialists generally agree that institutional care should be discouraged because it promotes psychological dependence and prevents children from interacting with their peers and integrating into society. Perhaps the strongest disadvantage, however, is the cost. The monthly cost per child in an institution for disabled children in Harare, for example, was US$80 in 1990, a cost that exceeded the monthly income of the majority of Zimbabwean families (House et al., 1990).

Some institutions have supported community-based approaches, as described in Box 3-8. Institutions that previously offered long-term residential care have been converted to boarding schools for severely disabled children, who return to their families during school vacations. Institutions can also provide short-term rehabilitation for rural children who require surgery or the fitting of appliances. Hospital rehabilitation departments that traditionally focused on the short-term rehabilitation of patients with an acute disability, particularly those at the district and provincial levels, now provide technical, administrative, and training support to community-based programs through outreach activities. Rehabilitation villages have been constructed in rural hospitals so that disabled children and their caregivers can be accommodated for group activities and workshops.

BOX 3-8

Rehabilitation of Disabled Children in Zimbabwe. Zimbabwe has a national strategy for rehabilitation of disabled children, which is coordinated through the health care system. Rehabilitation services are provided in communities, district hospitals, provincial (more...)

Primary health care model

The most comprehensive CBR model is based in the primary health care system and is supported by a national strategy for rehabilitation of children and adults with disabilities including those from birth defects. Rehabilitation in Zimbabwe is an example of this model of care (see Box 3-8).

Psychosocial support

Birth defects have serious lifelong consequences for both the patient and the family. Those afflicted require psychological, emotional, and social support on a continuing basis; this support should include referral to and assistance from social services such as education and social welfare. Many birth defects lead to death in infancy or early childhood, so care of the patient may also include terminal or palliative care.

Depending on the setting, care may be provided by a nurse, physician, or other health worker trained to provide appropriate support (see Box 3-6) (Christianson et al., 2000). These caregivers must provide the best locally available care for the patient and the family (World Health Organization, 1999; Christianson et al., 2000), including addressing their concerns and uncertainties. Patient and parent support groups can provide mutual assistance and support (World Health Organization, 1999).

Recommendation 11. Parents of children with birth defects should be guided to organizations that provide rehabilitation for the child and psychosocial support for the child and family. Education policies at the national and local levels should ensure that all children, including those with birth defects, receive appropriate schooling.

SCREENING FOR GENETIC DISORDERS

Over the past four decades, infant mortality in developing countries has declined, though there is still room for considerable improvement (Table 3-1).

TABLE 3-1

Improving Infant Mortality Rates in Developing Countries (1960–1999).

Once countries have successfully used the basic strategies of reproductive health care to reduce infant mortality, up to two-thirds of which is neonatal mortality (Hill, 1999), the more intractable causes of mortality and severe morbidity become the next challenge. Important among these are the more common genetic disorders for which screening becomes essential to further decrease infant mortality (World Health Organization, 2000a). Such programs are more demanding of resources and highly trained staff than are programs for basic reproductive health care; but, when introduced after basic reproductive health care services have reduced mortality, they too can be cost-effective. Screening programs were introduced in Cuba when the infant mortality rate (IMR), had been lowered to 19 per 1,000 live births (Heredero, 1992) and in Costa Rica (Saborio, 1992) at a similar IMR.

Genetic screening of populations identifies clinically normal individuals who have genotypes associated with a birth defect or who are at high risk of producing offspring with a birth defect. It aims to identify as many affected individuals as possible, but screening alone does not detect all individuals at high risk. Diagnosis usually follows a positive screening test and it provides a high level of accuracy. Examples of screening programs include those for α-thalassemia in Asian populations, β-thalassemia in Mediterranean populations, sickle cell disorder (SCD) in African populations, glucose-6-phosphate hydrogenase (G6PD) deficiency in female relatives of a patient with the deficiency, and chromosomal abnormalities in women over 35 years of age.

Genetic screening programs can involve preconceptional detection of risk factors associated with birth defects, also prenatal and neonatal screening and diagnosis of birth defects. The criteria for establishing screening programs for genetic disorders are presented in the next section, followed by a discussion of the important role of genetic counseling in any screening effort. The specific goals and methods of preconceptional, prenatal, and neonatal screening for birth defects follow, then ethical considerations of screening, diagnosis, and prevention or treatment.

Criteria for Establishing Genetic Screening Programs for Genetic Disorders

Screening programs need to be tailored to the health priorities of each community as determined by epidemiology, demographics, resources, and the capacity of health care services. The following prerequisites guide the determination of which birth defects can benefit from genetic screening (Simpson and Golbus, 1992; Cuckle and Wald, 2000):

• The target condition is serious and relatively common. Since individuals with less serious birth defects can live fulfilling lives, the conditions that are appropriate for screening are those that are serious or life threatening.
• Screening takes place at the best possible time. While screening may be conducted in the preconceptional, prenatal, or neonatal periods, the earlier a diagnosis is made, the more opportunities may be available to prevent a birth defect or minimize its severity.
• The screening assay clearly distinguishes between individuals who have the condition and those who do not. Since each birth defect is relatively rare, the assay should have a low false-positive rate.
• Effective and acceptable management strategies are available. Population screening and prenatal diagnosis for α- and β-thalassemia, sickle cell anemia, and phenylketonuria (PKU) are appropriate because there are management strategies for each.
• The program is cost-effective. Although the technology is available to screen for many disorders, not all screening is likely to be cost-effective in a given population or health care setting.

Thalassemia

β-Thalassemia major is easy to diagnose, and effective—though costly— treatment is available. Blood transfusions combined with iron chelating therapy allow many people with the disorder to survive into their twenties and thirties. A more expensive and higher-risk option—stem cell transplant from bone marrow or cord blood—can cure the disorder but is not affordable in low-income populations. Without diagnosis and treatment, patients with β-thalassemia major usually die early in childhood; thus, the population prevalence of β-thalassemia is a fraction of the birth prevalence, and the cost of treating the few people who survive to adulthood is low. Where diagnosis and treatment for β-thalassemia are available, patients survive longer, the population prevalence increases, and national treatment costs rise. Screening and control programs have significantly reduced the birth prevalence of β-thalassemia in Greece (Loukopoulous, 1996), Iran (see Box 3-9), and Sardinia (Cao et al., 1991, 1996).

BOX 3-9

Control of Thalassemia in Iran. Iran has a population of 67 million, is a middle-income country, and spends 6 percent of its gross national product on health services, which are exemplary (United Nations Children's Fund, 2000; Shadpour, 1994). Thirty (more...)

A premarital screening program in the Aegean region of Turkey tested nearly 10,000 couples over 4 years and found a β-thalassemia trait prevalence of 2.6 percent in that population. Prenatal screening of the same population identifies at-risk couples who are offered prenatal diagnosis and, in the case of pregnancies with β-thalassemia major, pregnancy termination (Keskin et al., 2000). Hospital-based prenatal screening programs in Thailand (Jaovisidha et al., 2000) identify pregnancies at risk for α- and β-thalassemias. At-risk couples are offered prenatal diagnosis and, if severe thalassemia is diagnosed, the option to terminate the pregnancy.

Sickle cell disorder

More than 60 percent of all births of children with SCD or other major hemoglobin disorders occur in Africa, the region with the most limited resources for addressing these conditions (Angastiniotis et al., 1995). Thus, while there are treatments for SCD, cost-effective measures to educate at-risk couples and communities about SCD and reduce the number of children born with sickle cell anemia (HbSS) appear to be important, but have not been recognized as a priority. To date, Cuba is the only country in Latin America (Angastiniotis et al., 1995) that has initiated a comprehensive control program for SCD; it is described in Box 3-10.

BOX 3-10

National Genetic Screening in Cuba. In 1981, in response to the increasing proportion of infant mortality and morbidity attributable to birth defects and the local development of appropriate diagnostic screening tests, Cuba initiated a national program (more...)

As with thalassemia, primary prevention of SCD can be achieved through preconceptional genetic screening and counseling of couples at risk for having a child with the disease, while secondary prevention can be provided through prenatal screening and counseling, which may be followed by prenatal diagnosis and the possibility of terminating affected pregnancies. Where genetic screening is not available, couples who have given birth to a child with SCD should be advised on the risk for future pregnancies.

Where screening for sickle cell trait and disease is undertaken, neonatal screening permits the early treatment of SCD. It also provides the opportunity to educate parents on the care of affected children and the risk for future pregnancies. The potential harm that could result from false-positive and false-negative results should be carefully considered.

Treatments for SCD include measures to reduce the symptoms and severity of anemia and prevent potentially fatal infections (penicillan prophylaxis and pneumococcal vaccine), to which SCD patients are especially susceptible (Lees et al., 2000; Steensma et al., 2001). Hydroxyurea can prevent vaso-occlusive crises (Koren et al., 1999), but the drug is expensive (Charache et al., 1995; Kate, 2001; Davies and Oluhohungbe, 2002). Bone marrow transplantation is available in high-resource settings (Kate, 2001), but rarely in developing countries. Some homozygotes with high levels of fetal hemoglobin may need little more than long-term folate supplementation, while others require aggressive supportive care, frequent hospitalizations, pain relief, and transfusions (Steensma et al., 2001). Pulmonary symptoms require immediate attention since acute chest syndrome is a major cause of death (Vichinsky et al., 1997).

In some developing countries, SCD goes largely undiagnosed and leads to high mortality during the first 5 years of life (Akinyanju, 1989; Angastiniotis et al., 1995). Under such circumstances, health education is a priority, since there is no chance for prevention or treatment in populations where SCD is not recognized and diagnosed. Where treatment for SCD is unavailable—such as in tribal areas of Maharashtra, India—a combination of health education and genetic screening has been suggested as the most effective means of reducing the impact of SCD (Kate, 2001).

Glucose-6-phosphate dehydrogenase deficiency

The primary effects of G6PD deficiency are hematological (Verjee, 1993), so most interventions focus on reducing the occurrence and severity of hemolytic crises. These episodes can be precipitated by infections such as hepatitis or pneumonia; exposure to certain chemicals and oxidative medications, including some antimalarial drugs; and consumption of fava beans (Chatterjea, 1966; Meloni et al., 1992; Beutler, 1994; Verjee, 1993). Avoiding these triggers for hemolysis requires that affected persons be diagnosed and counseled. Occasionally those with the Mediterranean form of the deficiency and those in hemolytic crisis require a blood transfusion.

Elevated bilirubin levels, elevated reticulocyte count, and low red blood cell count and hemoglobin levels are signs of G6PD deficiency. In the neonate, hyperbilirubinemia may be severe and, if left untreated, can cause bilirubin encephalopathy. Screening tests—fluorescent spot test, ascorbate cyanide test, MTT staining test, methemoglobin reduction methods, and dye decolorization (Verjee, 1993)—are quick, easy, inexpensive, and suitable for large populations. The diagnosis is confirmed by enzyme assay (Meloni, 1992), but the definitive assay requires laboratory equipment that is not usually available in the countries where G6PD deficiency is common.

Cystic fibrosis

Screening the family members of a patient with cystic fibrosis (CF) can detect the CF gene in 60–90 percent of carriers (Grody et al., 2001), which allows informed reproductive choices to be made (Frossard et al., 1999). An early diagnosis is key for prevention of CF since many high-risk couples have a second affected child before the diagnosis has been established for the first child (Rabbi-Bortolini et al., 1998). Prenatal screening programs have not become routine even in developed countries (Haddow et al., 1999).

The most important diagnostic test for CF in developing countries is the sweat electrolytes test (Mahashur, 1993). Screening tests include DNA testing, fecal fat, upper gastrointestinal and small bowel series, and measurement of pancreatic function. In Latin America, CF is underdiagnosed because of high mortality rates from pulmonary and gastrointestinal diseases and limited access to the sweat test (Macri et al., 1991).

Ideally, treatment of CF would involve a multidisciplinary team (physician, physiotherapist, nutritionist, and social worker) to provide conventional therapy (antibiotics, pancreatic enzyme replacement by ingestion of capsules with meals, and nutritional support) and treatment for CF-associated complications (Mahashur, 1993; Zar et al., 1998). Such an intensive approach is not available or cost-effective in many settings.

Phenylketonuria

Screening for PKU is done with the relatively inexpensive Guthrie test on filter paper blood specimens. The timing of the screening is critical, so the specimen should be obtained in the hospital of birth as close to discharge as possible. Because second tests are unlikely to detect new cases, resources are best directed at improving the primary screening (Cunningham, 2000). In countries where the incidence of PKU is relatively high, such as Estonia (Ounap et al., 1998), and Latvia (Lugovska et al., 1999)—1 per 6,010 and 1 per 8,700 respectively—there are mass screening programs, while in countries, such as South Africa, where the incidence is low (Hitzeroth, 1995)—1 per 20,000—there are more pressing health priorities. The number of infants born at home and thus not diagnosed is undetermined.

The mainstay of treatment is a phenylalanine-restricted diet. By limiting daily consumption to only 250–500 milligrams of phenylalanine per day, a positive nitrogen balance and safe plasma levels of phenylalanine can be maintained. The amino acid supplements, which are taken with vitamin and mineral supplements are not palatable, which makes compliance with the restricted diet difficult (Cunningham, 2000; Poustie and Rutherford, 2001). The diet should begin as soon after birth as possible and be continued as long as the patient is able to comply. While a phenylalanine-restricted diet has been shown in nonrandomized studies to reduce blood phenylalanine levels and improve IQ and neuropsychological outcome, the evidence is inadequate for determining a safe upper level of phenylalanine and when, if ever, dietary restrictions can be relaxed (Poustie and Rutherford, 2001).

Because early dietary treatment has proven successful, affected women now become potential mothers (Cunningham, 2000). Avoiding mental retardation and other problems in their offspring requires that they resume the restricted diet prior to and throughout pregnancy to avoid phenylalanine levels that would be toxic to the fetus and cause severe mental retardation, birth defects, heart disease, and low birth weight.

Hemophilia A and B

Because hemophilias A and B are relatively uncommon, prenatal screening should be restricted to families with a history of the disorder. A fetal blood sample can be used for diagnosis of genetic disorders of red cells, white cells, or platelets and for identification of clotting factor deficiencies. Amniocentesis, chorionic villus sampling, or a placental biopsy are used to obtain cells for cytogenetic or biochemical analysis and to isolate fetal DNA (Weatherall and Letsky, 2000). Male patients with severe hemophilia are often diagnosed shortly after birth because of an extensive cephalohematoma or profuse bleeding at circumcision. Neonates suspected of having hemophilia should receive screening tests for hemostasis, including a platelet count, bleeding time, and blood clotting ability (Handin, 1998).

Treatment is complicated and expensive, which limits its usefulness for most developing countries. In Turkey, a program using intermediate concentrates rather than high-purity concentrates or recombinants and a twice-weekly regimen (instead of three times a week) reduced the cost of therapy (Kavakli et al., 1997). A rehabilitation center in India has reported a program for preventing and treating acute hemarthrosis in which the patient is taught a series of exercises that facilitate absorption of the hematoma to improve joint range and strengthen muscles, which reduces the frequency of bleeding (Kale, 1999).

Many centers have organized home care programs so that patients can administer their own factor VIII infusions with the onset of symptoms (Handin, 2001). Local health clinics can give injections to hemophiliacs. Home and local care spare limited health personnel resources and solve problems of transportation and absenteeism from school and work. Hemophiliacs are at high risk for HIV/AIDS and hepatitis B if a safe supply of blood products is not maintained. An alternative may be to import blood products.

Preconceptional Screening

Preconceptional screening has the advantage of identifying and counseling couples at high risk for producing a child with a birth defect before conception. The screening has three components: recording and evaluation of a genetic history, laboratory testing where indicated, and counseling. Genetic histories can identify clinically normal couples at risk for passing an inherited birth defect to their offspring and carriers of abnormal recessive genes who are at risk of passing a disorder to their children. Individuals at high risk can be screened and, if determined to be at risk, should receive counseling and other appropriate care (see Box 3-11).

BOX 3-11

Indications for Preconceptional Genetic Consultation. Indication – Previous pregnancy history

A genetic history explores whether a couple is at risk for inherited disorders or for chromosomal abnormalities or mutations that could result in birth defects. Maternal age over 35 years is the most common risk factor for chromosomal abnormalities. Paternal age over 40 years increases the risk of certain dominant mutations (McIntosh et al., 1995). Exposure to mutagenic agents should also be determined. Abnormal reproductive outcomes (repeated spontaneous abortions, stillbirths, and infants born with birth defects) among first-degree relatives (siblings, parents, offspring), second-degree relatives (uncles, aunts, nephews, nieces, and grandparents), and third-degree relatives (first cousins) are reviewed. Identification of second- and third-degree relatives with birth defects generally does not increase a couple's risk significantly unless the couple is consanguineous. The ethnic origin of each potential parent should be noted because of the higher risk for certain birth defects among particular groups. Genetic histories can be recorded efficiently using a questionnaire that requires only positive responses (Simpson and Golbus, 1992).

Preconceptional screening of national populations or high-risk groups has been undertaken in countries where serious recessive birth defects are prevalent, a reliable test is available, and the condition is amenable to prevention. Conditions that are common in the developing world and amenable to prevention include thalassemia and SCD. National screening is performed in Greece, Iran (see Box 3-9), Sardinia, and Cyprus for β-thalassemia and in Cuba for SCD (see Box 3-10). Family planning services provide an ideal setting for genetic screening and the use of genetic histories for the preconceptional prevention of birth defects.

NATIONAL COORDINATION, SURVEILLANCE, AND MONITORING

The impact of individual birth defects and of birth defects in the aggregate must be known with some accuracy if priority needs are to be identified and addressed. Epidemiological data can establish the prevalence and health burden associated with birth defects and provide information for establishing priorities for interventions. Regular surveillance provides trends and monitors the clinical- and cost-effectiveness of interventions. The assessment of neonatal mortality due to birth defects is difficult and expensive, however, since most deliveries in developing countries take place at home, and infant deaths that occur during or shortly after childbirth are rarely recorded in official statistics. As a result, data on total infant mortality and mortality due to birth defects vary widely and are almost certainly underestimates.

Developing countries differ widely in their needs and resources for the establishment of data systems. Further, establishment of a monitoring system competes for limited resources with interventions to reduce birth defects. However, even relatively simple efforts to monitor the birth prevalence of common birth defects (see Box 3-12), along with associated death and disability, can highlight priority areas and changes in those areas over time. This information is key to identifying priority interventions and to their success over time.

BOX 3-12

Community-Based Genetic Screening Services in Rural South Africa. In 1985 only 25 percent of the 5,000 patients seen at genetic clinics were black South Africans, who at that time constituted 75 percent of the population. Limited epidemiological information (more...)

Recommendation 13. Collection of epidemiological data on birth defects is necessary to understand the extent of the problem and identify intervention priorities. Depending on the infant mortality rate, the capacity of the health care system, and the resources available, countries should incrementally develop the following:

• National demographic data on neonatal and infant mortality and morbidity,
• Data on causes of death,
• Documentation of birth defects using standardized protocols for diagnosis, and
• Ongoing monitoring of the common birth defects in a country or region.

Many organizations and parts of government can contribute to the strengthening of health care in developing countries. National leadership and coordination of these organizations and capabilities can vastly improve the quality and equity of health care, including reproductive health care and care of birth defects.

Recommendation 14. Each country should develop a strategy to reduce the impact of birth defects, a framework of activities by which this can be accomplished, and the commitment of health leaders to accomplish these goals.

National programs of basic reproductive health should collect and interpret surveillance data, set uniform standards for the training and performance of health care providers, and foster communication among health care providers, researchers, and policy makers.

Recommendation 15. Each country should strengthen its public health capacity for recognizing and implementing interventions that have proven effective in reducing the impact of birth defects. This includes monitoring and tuning interventions for clinical- and cost-effectiveness in the local setting.

CONCLUSION

Despite the existence of low-cost interventions for preventing and treating a number of birth defects, the human, economic, and social burdens associated with these conditions remain high. Obstacles to improving care for birth defects include financial constraints; lack of knowledge on the part of health care workers; poor access to medical facilities; and issues surrounding ethnicity, language, religion, and culture. Governments must be educated on the cost-effectiveness of reducing the impact of birth defects through proven methods of prevention and care, which can be adapted to local resources and needs. Providing the best possible care for patients with birth defects begins with the recognition that such care may require significant financial commitment and that the care that can be provided will vary with the setting (World Health Organization, 1985, 1997, 1999; Carey, 1992).

Robust programs of basic reproductive health care and public health campaigns provide a framework for new efforts to reduce the impact of birth defects. Reducing the impact of birth defects in developing countries can be approached through a three-stage process. The first stage of the process involves low-cost interventions to prevent specific birth defects. The second stage addresses improved treatment and rehabilitation for those with birth defects. Although generally more costly than the first stage preventive interventions, reducing the disease burden for those with birth defects, is key to providing equitable health care as these individuals can suffer from both the burden of disease and an associated burden of lost social and economic opportunity. The third stage is important for countries with comprehensive systems of basic reproductive health care and lower IMRs. The screening and diagnosis of genetic disorders can further reduce infant mortality when they are tailored to national health priorities and address common and severe birth defects that can be accurately detected and effectively prevented or managed. Counseling, with the goal of enabling individuals to make free and informed health care decisions, is an essential part of screening and diagnostic programs.

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Footnotes

1

A 10-week gestation corresponds to 8 embryonic weeks after conception.