Birth Defects

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Birth defects

Birth defects, also known as congenital malformations, are structural or metabolic abnormalities present at birth. While subtle variations from the normal, of no clinical interest, occur in about half of all individuals in the United States, significant congenital defects are found in about 3% of live births. Fortunately, only about half of these require medical attention.

Birth defects may result from genetic causes or environmental insult. Defective genes are not easily repaired and thus are perhaps less interesting than teratogenic substances to environmentalists. It is theoretically possible to limit exposure to teratogens by elimination of the agent in the environment or by modification of behavior to prevent contact. It should be noted, however, that the causes of more than half of congenital malformations remain unknown.

Birth defects of genetic origin may be due to aberrant chromosome number or structure, or to a single gene defect. Normal humans have 46 chromosomes, and variation from this number is referred to as aneuploidy. Down's syndrome, an example of aneuploidy, is usually characterized by an extra chromosome designated number 21. The Down's individual thus has a total of 47 chromosomes, and the presence of the extra chromosome results in multiple defects. These include mental retardation and physical characteristics comprising a small round head, eyes that slant slightly upward, a large and frequently protruding tongue, low set ears, broad hands with short fingers and short stature. People with Down's syndrome are particularly vulnerable to leukemia . Children with this condition are rarely born to mothers less than 25 years of age (less than one in 1,500), but the prevalence of Down's syndrome babies increases with mothers older than 45 (about one in 25). Down's syndrome can be detected during pregnancy by chromosome analysis of fetal cells. Fetal chromosomes may be studied by chorionic villus sampling or by amniocentesis.

Other congenital abnormalities with a chromosomal basis include Klinefelter's syndrome, a condition of male infertility associated with an extra X chromosome, and Turner's syndrome, a condition wherein females fail to mature sexually and are characterized by the aneuploid condition of a missing X chromosome. Achondroplasia is a birth defect due to a dominant mutation of a Mendelian gene that results in dwarfism. Leg and arm bones are short but, the trunk is normal and the head may be large. Spontaneous mutation accounts for most achondroplasia. The mortality rate for affected individuals is so high that the gene would be lost if it were not for mutation. Albinism, a lack of pigment in the skin, eyes, and hair, is another congenital defect caused by a single gene, which in this case is recessive.

The developing fetus is at risk for agents which can pass the placental barrier such as infectious microbes , drugs and other chemicals , and ionizing radiation . Transplacental teratogens exert their effect on incompletely formed embryos or fetuses during the first three months of pregnancy. Organs and tissues in older and full term fetuses appear much as they will throughout life. It is not possible to alter the development of a fully formed structure. However, prior to the appearance of an organ or tissue, or during the development of that structure, teratogenic agents may have a profoundly deleterious effect.

Perhaps the best known teratogen is the sedative thalidomide which induces devastating anatomical abnormalities. The limb bones are either shortened or entirely lacking leading to a condition known as phocomelia. Intellectual development of thalidomide babies is unaffected. The experience with this drug, which started in 1959 and ended when it was withdrawn in 1961, emphasizes the fact that medications given to pregnant mothers generally cross the placenta and reach the developing embryo or fetus. Another drug that effects developmental abnormalities is warfarin which is used in anticoagulant therapy. It can cause fetal hemorrhage, mental retardation, and a multiplicity of defects to the eyes and hands when given to pregnant women.

The teratogenic effects of alcohol, or the life style that may accompany alcohol abuse, serve to illustrate that the term environment includes not only air and water but the personal environment as well. Alcoholism during pregnancy can result in "fetal alcohol syndrome" with facial, limb, and heart defects accompanied by growth retardation and reduced intelligence. The effects of alcohol may be magnified by factors associated with alcoholism such as poor diet, altered metabolism and inadequate medical care. Because neither the time of vulnerability nor the toxic level of alcohol is known, the best advice is to eschew alcohol as a dietary constituent altogether during pregnancy.

Disease of the mother during pregnancy can present an environmental hazard to the developing fetus. An example of such a hazard is the viral disease German measles, also known as rubella. The disease is characterized by a slight increase in temperature, sore throat, lethargy and a rash of short duration. Greatest hazard to the fetus is during the second and third month. Children born of mothers who had rubella during this period may exhibit cataracts, heart defects, hearing loss and mental retardation. Obviously, the virus transverses the placenta to infect the embryo or fetus and that infection may persist in the newborn. Birth defects associated with rubella infection have decreased since the introduction of a rubella vaccine.

The most common viral infection that occurs in human fetuses is that of a herpes virus known as cytomegalovirus. The infection is detected in about 1–2% of all live births. Most newborns, fortunately, do not manifest symptoms of the infection. However, for a very small minority, the effects of congenital cytomegalovirus are cruel and implacable. They include premature birth or growth retardation prior to birth, frequently accompanied by hepatitis, enlarged spleen, and reduction in thrombocytes (blood cells important for clotting). Abnormally small heads, mental retardation, cerebral palsy, heart and cerebral infection, bleeding problems, hearing loss and blindness occur. Exposure of the fetus to the virus occurs during infection of the pregnant woman or possibly from the father, since cytomegalovirus has been isolated from human semen.

Other infections known to provoke congenital defects include herpes simplex virus type II, toxoplasmosis, and syphilis.

Methylmercury is an effective fungicide for seed grain. Accidental human consumption of food made from treated seeds has occurred. Industrial pollution of sea water with organic mercury resulted in the contamination of fish, consumed by humans, from Minamata Bay in Japan. It has been established that organic mercury passes the placental barrier with effects that include mental retardation and a cerebral palsy-like condition due to brain damage. Anatomical birth defects, engendered by organic mercury, include abnormal palates, fingers, eyes and hearts. The toxicity of methylmercury affects both early embryos and developing fetuses. Exclusion of mercury from human food can be effected by not using organic mercury as a fungicide and by ending industrial discharge of mercury into the environment.

Of course other chemicals may be hazardous to the offspring of pregnant women. Polychlorinated biphenyl (PCB)s, relatively ubiquitous but low level oily contaminants of the environment, cause peculiar skin pigmentation, low birth weights, abnormal skin and nails, and other defects in offspring when accidentally ingested by pregnant woman.

Uncharacterized mixtures of toxic chemicals which contaminate the environment, are thought to be potential teratogens. Cytogenetic (chromosomal) abnormalities and increased birth defects were detected among the residents of Love Canal , New York. Cigarette smoke is the most common mixture of toxic substance to which fetuses are exposed. Tobacco smoke is associated with reduced birth weight but not specific birth anatomical abnormalities.

Much concern has arisen over the damaging effects of ionizing radiation, particularly regarding diagnostic x-rays and radiation exposure from nuclear accidents. The latter concern was given international attention following the explosion at the Ukraine's Chernobyl Nuclear Power Station in 1986. Fear that birth defects would occur as a result was fueled by reports of defects in Japanese children whose mothers were exposed to radiation at Hiroshima. Scientists believe that radiation to the fetus can result in many defects including various malformations, mental retardation, reduced growth rate and increased risk for leukemia. Fortunately, however, the risk of these effects is exceptionally low. Fetal abnormalities caused by factors other than radiation are thought to be about 10 times greater than those attributed to radiation during early pregnancy. However small the risk, most women choose to limit or avoid exposure to radiation during early pregnancy. This may be part of the reason for the increased popularity of diagnostic ultrasound as opposed to x ray.

While concern is expressed for particular teratogenic agents or procedures, the etiology of most birth defects is unknown. Common defects, with unknown etiology, include hare lip and cleft palate, extra fingers and toes, fused fingers, extra nipples, various defects in the heart and great vessels, cerebral palsy (sometimes as a result of difficult labor and delivery but frequently for no known cause), narrowing of the entrance to the stomach, esophageal abnormalities, spina bifida, clubfoot, hip defects, and many, many others. Since the majority of birth defects are not caused by known effects of disease, drugs, chemicals or radiation, much remains to be learned.

[Robert G. McKinnell ]