Reducing Birth Defects Meeting the Challenge in the Developing World (2003) / Chapter Skim
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2 Impact and Patterns of Occurrence
2 Impact and Patterns of Occurrence
Pages 22-67
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From page 22... ...
Many developing countries lack health-related statistics and registries, and about one-third of all births in these countries an estimated 40 million each year are not registered (Murray and Lopez, 1996; World Health Organization, 1997, 1999; United Nation Children's Fund, 19981. Thus in much of the world, it is difficult to calculate the birth prevalence of birth defects with any precision because the number of infants afflicted and the total number of surviving infants born within a specified time period is not measured.
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(see Box 2-11; the Latin American Collaborative Study of Congenital Malformations (ECLAMC) (see Box 2-21; the Chinese Birth Defects Monitoring Program (CBDMP)
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This occurs more commonly in countries that lack family planning and access to contraceptives (WorId Health Organization, 19991. As Table 2-1 shows, the risk of chromosomal abnormalities, and of Down syndrome in particular, increases rapidly with advancing maternal age (Hook, 19811.
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Congenital heart disease associated with Down syndrome can be fatal and is the major cause of death. Inadequate
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The condition causes multiple malformations, profound mental retardation, and usually death in the first few months. It occurs in about 1 per 8,000 live births (Hook, 1992)
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Pregnancies from consanguineous marriages marriages generally of first cousins and inclucling second cousins have an increased birth prevalence of autosomal recessive diseases, which increases the risk of stillbirth, neonatal and chilc~hooci cleath, mental retardation, and birth defects compareci with pregnancies among unrelated couples (Jaber et al., 1992~. In most Western urban populations, the frequency of consanguineous marriages (Castilla et al., 1991)
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From page 28... ...
genes are believed to have originated in Africa, Asia, and the Mediterranean basin and may have remained at high frequencies because of the previously noted selective advantage of malaria resistance conferred on the heterozygous carriers of such genes, who do not usually exhibit symptoms of thalassemia (Weatherall, 1997; Sweeting et al., 19981. Thalassemias are generally more prevalent than sickle cell disorders in the Eastern Mediterranean region, North Africa, South Asia, East Asia, and the Pacific.
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From page 29... ...
oc-Thalassemia is most prevalent in Asia. Several populations have been screened to determine the prevalence of thalassemia genes and traits (see Appendix A, Table A-31; or and p-thalassemia have a high incidence in a broad geographical band extending across the Mediterranean basin and parts of Africa, through the Middle East, and across India, Southeast Asia, and the Pacific Islands (see Figure 2-11.
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From page 30... ...
with another abnormal hemoglobin. Heterozygote carriers have the largely asymptomatic sickle cell trait (HbAS)
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From page 31... ...
Relatively high rates of consanguineous marriage in the Eastern Mediterranean region have increased the prevalence of sickle cell disease in that population as well (WorId Health Organization, 1997~. Children with homozygous sickle cell disease or sickle cell anemia are susceptible to episodes of painful vaso-occlusive crises and chronic anemia and are at increased risk for developing infections, particularly Streptococcus pneumoniae, which can cause fatal sepsis, meningitis, or pneumonia.
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From page 32... ...
The disorder is most prevalent in Central, West, and East Africa; the Eastern Mediterranean; and South and East Asia (Verjee, 1993; El-Hazmi and Warsy, 1 996; World Health Organization, 1 989, 1996, 1997~. As with thalassemias and sickle cell disease, carriers of G6PD deficiency have a selective advantage against infection by malaria (Roth et al., 1983)
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From page 33... ...
and 1 per 3,000 live births in Turkey (Gurson et al., 19731. African-American CF patients were shown to have a different mutation profile from white CF patients; then a South African study identified different mutations in populations of African origin and predicted the incidence of CF to range from 1 in 784 to 1 in 13,924 births in this population (Padoa et al., 19991.
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From page 34... ...
Affected neonates appear normal at birth but lose interest in their surroundings at 3 to 6 months of age and exhibit severe mental retardation by 1 year. Other clinical findings include an eczematous rash, microcephaly, growth retardation, and decreased pigmentation of hair and skin.
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. conversion in pregnancy Not known scars Rubella Eye and heart defects; 90% after serologically deafness; neurological confirmed infection of damage mother in first 10 weeks of pregnancy Toxoplasmosis Neurological damage; 30-40% after maternal eye disorder; deafness seroconversion in pregnancy without treatment Other maternal diseases: Neurological damage; Microcephaly in 8.5% of Phenylketonuria cardiac defects phenyketonuric infants with blood phenylalanine >1.2 nmol/L Insulin-dependent Cardiovascular and Major defects in 8% of diabetes mellitus central nervous system infants of affected women (CNS)
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From page 36... ...
36 TABLE 2-2 continued REDUCING THE IMPACT OF BIRTH DEFECTS Teratogen Main Defects Caused Estimated Risk Coumarin derivatives Nasal hypoplasia; Nasal hypoplasia or epiphyseal stippling; epiphyseal stippling in 8% neurological damage after use in first trimester; brain damage in 5% after use in second trimester Diethylstilbestrol Genital anomalies Testicular anomalies, epididymal cysts, or penile hypoplasia in up to 20% of males, and ridges in cervix and/or vagina in up to 40% of females exposed to a dose of 150 mg between 7 and 34 weeks' gestation Folic acid antagonists Craniofacial defects 40% after aminopterin in (aminopterin, first 10 weeks of pregnancy; methotrexate) not known for methotrexate Lithium Cardiac defects, 3% especially Ebstein's anomaly Retinoids Microtia-anotia; CNS, 20% after isotretinoin in cardioaortic, and first trimester thymic defects Thalidomide Reduction deformities 50% after use in first 8 of limbs weeks of pregnancy Recreational drugs: Cocaine Urinary tract defects Major defects in 5% of users of cocaine with or without other drugs Alcohol Neurological damage; 30% of infants of women cardiac and joint with manifest chronic defects alcoholism Environmental pollutants: Neurological damage 6% of infants in fishing Methylmercury village where seafood was contaminated Miscellaneous: Iodine deficiency Neurological damage; 40% of surviving infants in deafness iodine-deficient area whose mothers' blood total thyroxine was <25 ng/mL Ionizing radiation Neurological damage Microcephaly in 70% after estimated dose >1.5 gy from atomic bombs in first 18 weeks of pregnancy SOURCE: Adapted from Leck, 1994.
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The resulting birth defects blindness, deafness, cardiovascular anomalies, and mental retardation are referred to collectively as congenital rubella syndrome (CRS)
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From page 38... ...
In unimmunized populations, rubella epidemics occur on average every 4 to 7 years (Cutts et al., 1997~. Over the last 25 years, surveillance of these epidemics has documented CRS birth prevalence rates of 0.6-2.2 (Banatvala, 1998)
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From page 39... ...
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From page 40... ...
Over 90 percent of the infected infants are asymptomatic at birth, but 5-17 percent of them will later develop sensorineural hearing loss, chorioretinitis, mental retardation, and neurological damage. Nearly 90 percent of the infants with symptoms at birth will develop severe abnormalities associated with damage to the central nervous system (CNS)
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From page 41... ...
Long-term sequelae include mental retardation, seizures, severe visual impairment, blindness, and hearing impairment. Herpes simplex virus (HSV)
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From page 42... ...
Phenylketonuria This is an autosomal recessive disorder carrying a significant risk that affected infants will also have disorder, a congenital malformation, or neurological impairment (see the earlier discussion under single-gene disorders)
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From page 43... ...
In 1990, it was estimated that 43 million people worldwide live with cretinism, mental retardation, and brain damage due to IDD (United Nations Children's Fund, 1998~. In endemic areas, where up to 100 percent of the population fails to consume adequate iodine (All, 1995; Wyss et al., 1996; Yusuf et al., 1996; Geelhoed, 1999; Kouame et al., 1998)
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From page 44... ...
The mean IQ scores in the iodine-deficient group were 13.5 points lower than in the control group. This would suggest that the widespread effect of iodine deficiency on brain function and learning ability has profound implications for the economic and manpower development of affected populations (Dunn, 1994~.
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Neural tube defects (NTDs) CNS malformations, secondary cancer Masculinization of female fetuses Vaginal carcinoma and other genitourinary defects in female and male offspring Neonatal hypoglycemia Ebstein's anomaly Moebius sequence Constriction of the ductus arteriosus,C necrotizing enterocolitis Facial and CNS defects Growth retardation, CNS defects Neonatal withdrawal syndrome when drug is taken in late pregnancy CNS, craniofacial, cardiovascular, and other defects Anomalies of teeth and bone Limb-shortening defects, internal organ defects Facial and CNS defects NTDs Skeletal and CNS defects, Dandy-Walker syndrome 45 Drug Aminopterin,b methotrexate Angiotensin-converting enzyme inhibitors Anticholinergic drugs Antithyroid drugs (propylthiouracil and methimazole)
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47 ~ s-^ ~ U. Cd ~ a hi' ~ ~ =0, ~ ' ° a a ~ ~ :5 ' O =~ ~~ · ~ a 5 .= Cat 5, ·, ~ At, ~ .
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From page 48... ...
Fetal exposure, particularly during the first trimester, to derivatives of coumarin such as Coumadin (warfarin) can cause nasal hypoplasia, stippling of bones, optic atrophy, microcephaly, and growth and mental retardation.
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From page 49... ...
FAS encompasses a constellation of physical abnormalities, including alterations in facial features and fetal growth reduction, as well as behavioral and cognitive effects (Institute of Medicine, 19961. With or without the recognized dysmorphologic pattern known as FAS, mental retardation is the most serious and constant effect of alcohol use during pregnancy.
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From page 50... ...
Ionizing Radiation Studies of atomic bomb survivors demonstrated that exposure to ionizing radiation during gestation can damage the developing brain, particularly when exposure occurs 8 to 25 weeks after ovulation (Schull and Otake, 19991. Diagnostic radiography involves a low level of X-ray expo
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These conditions were selected for discussion because of their documented disease burden in developing countries. Neural Tube Defects These encompass a range of congenital malformations that result from incomplete development of the brain and spinal cord or their protective coverings.
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From page 52... ...
Because congenital heart disease is often not recognizable at birth, studies have used a wide range of ascertainment methods (Shibuya and Murray, 19981. Cleft Lip and/or Cleft Palate These are congenital malformations involving a gap in the soft palate and roof of the mouth, sometimes extending through the upper lip.
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From page 53... ...
Half of all infants with cleft lip and/or palate have additional birth defects, such as heart malformations, that co-occur as genetic syndromes (Shibuya and Murray, 19981. Birth prevalence rates for oral clefts from several countries are shown in Appendix A (Table A-ll)
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From page 54... ...
This position, which stabilizes the femoral head deep within the acetabulum, may correct many cases of congenital hip instability, preventing them from developing into dislocation (Edelson et al., 1984~. CONCLUSION Birth defects impose a severe disease burden worldwide: they affect all major body systems and cause fetal deaths, neonatal and childhood deaths, and severe and lifelong disabilities.
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From page 55... ...
1990. Congenital and perinatal cytomegalovirus infections.
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From page 56... ...
allele and sickle cell disease: A HuGE REVIEW. American Journal of Epidemiology 151(9)
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ECLAMC-Down survey Group. Latin American Collaborative Study of Congenital Malformations.
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:281288. ECLAMC (Latin American Collaborative Study of Congenital Malformations)
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1999. Prevalence of herpes simplex virus types 1 and 2, cytomegalovirus, and varicella-zoster virus infections in Eritrea.
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American Journal of Medical Genetics 44(1)
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1987. Lowered immunity status of rubella virus infection in pregnant women.
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2000. Epidemiology of fetal alcohol syndrome in a South African community in the Western Cape Province.
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American Journal of Tropical Medicine and Hygiene 41(2)
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1991. Rubella and congenital rubella syndrome in developing countries.
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From page 65... ...
American Journal of Medical Genetics 95(4)
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From page 66... ...
2001. Alcohol dehydrogenase-2~2 allele is associated with decreased prevalence of fetal alcohol syndrome in the mixed-ancestry population of the Western Cape Province, South Africa.
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From page 67... ...
Effects of consanguinity. American Journal of Medical Genetics 68(4)
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