Excerpted from When Your Child Has a Disability: The Complete Sourcebook of Daily and Medical Care, Revised Edition, edited by Mark L. Batshaw, M.D.

Copyright © 2001 by Paul H. Brookes Publishing Co. All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.

Andrew
Andrew, a friendly and vivacious 6-year-old, had always been slow to develop, and his language was more severely affected than his other skills. He was diagnosed as having moderate mental retardation at 4 years of age and was also noted to have marked hyperactivity. His pediatrician explained to Andrew's parents that he wanted to consider genetic testing. The pediatrician also felt that Andrew had a somewhat unusual face, dissimilar from that of his parents but very similar to that of his 8-year-old brother Mitchell, who at age 3 also had been diagnosed with developmental delays. The brothers' faces were long, and their ears were large and protruding. Both boys had a heart murmur suggesting a mild problem in a heart valve. Because these brothers had similar delays and features suggestive of a specific genetic dis-order, blood was obtained for a specific DNA (deoxyribonucleic acid) test for fragile X syndrome . Andrew and Mitchell were subsequently found to have fragile X syndrome. Although this knowledge did not open up any new treatment options, it did provide the family with information about long-term outcomes and encourage them to join a parent support group.

Prenatal Causes of Developmental Disabilities

Most severe developmental disabilities have their origin before birth, either as a result of a genetic or a chromosomal disorder, exposure to damaging substances in the environment, maternal infections, or yet unknown reasons. With so many opportunities for things to go wrong, one might wonder not why so many children have developmental disabilities but why so few do. It is important to understand that although there are many causes of disabili-ties, each is so rare that the total number of children affected is small. About 95% of all children are born without disabilities.

Genetic and Chromosomal Disorders

Genetic disorders occur in the sperm or the egg and may affect the formation of the fetus or the production of a specific product needed for typical growth and development. The most common genetically transmitted developmental disability is Down syndrome. Asecond group of inherited disorders involves defects in a single gene within a chromosome. This can lead to production of less enzyme as is found in inborn errors of metabolism such as phenylketonuria, in which a toxin builds up that leads to brain damage if untreated, and in neuromuscular disorders such as muscular dystrophy, in which an important muscle protein is missing. Impaired brain development is the problem in another single-gene defect, fragile X syndrome.

Environmental Causes

Other forms of prenatal brain damage have an environmental basis. Certain substances taken in by the mother during pregnancy can harm the fetus; these are called teratogens. Susceptibility to the teratogen depends on the dose and timing of the exposure. If exposure occurs close to conception, it generally has an all-or-none effect; the embryo survives unaffected or dies. At the other extreme, late in the pregnancy, the teratogen may affect the size of the fetus or may precipitate premature birth but will not cause a birth defect. The most damage is likely to be done by teratogens in the first trimester, when the body organs are forming.

An extreme example of the effect of teratogens occurred in pregnant women who survived atomic bomb blasts in Hiroshima and Nagasaki. These women received massive exposure to radiation (1,000 rad or more). Those exposed shortly after conception generally had miscarriages early in their pregnancies. Those exposed around 2-4 months' gestation gave birth to babies with small heads and mental retardation. Those exposed in the third trimester tended to have babies who were born prematurely.

In contrast, medical X-rays expose a woman to very small doses of radiation; for example, a chest X-ray produces less than 0.0001 rad. Because it is unknown what amount of radiation is safe for the fetus, doctors generally avoid exposing pregnant women to medical X-rays, especially during their first trimester of pregnancy. Ultrasound and microwaves, unlike X-rays, can-not cause damage to the fetus.

Medications

A number of medications have been associated with fetal malformations. The most disastrous example occurred in the late 1950s when thalidomide was introduced in Europe to treat the nausea that can occur with pregnancy. Hundreds of infants were born with shortened limbs before the link with thalidomide was established and the drug was removed from the market. Other medications, such as most antiepileptic drugs, have been shown to damage the fetus. Potential effects of these drugs include malformations of the baby's face, arms, legs, and spine, often with developmental delay. However, only about 10%- 20% of children whose mothers take these medications are affected, and the effects appear to be more severe when the dosage is high and when medication is taken early in pregnancy. Anticancer drugs can also produce fetal malformations because they are meant to kill the most rapidly dividing cells, which are found in a pregnant woman's embryo as well as her tumor.

Vitamins generally do not cause problems during pregnancy, and multivitamins are in fact recommended for all pregnant women. However, massive doses of orally administered vitamin A contained in the acne medication Accutane (isotretinoin) and the psoriasis drug Tegison (etretinate) have re-sulted in face and brain malformations in infants. Although there has been concern about other drugs, the medications just mentioned are the only ones in general use that have been shown conclusively to cause fetal malformations. Women should try, however, to take as few medications as possible during pregnancy, especially during the first trimester.

Substance Abuse

The drug most commonly associated with fetal malformations is not a prescription medication; it's alcohol. Approximately one third of women with alcoholism give birth to babies who have a spectrum of impairments called fetal alcohol syndrome (or its milder form, fetal alcohol effects), which may include mental retardation or learning and emotional disabilities, deformed limbs, a small head, and congenital heart defects. The degree of malformation depends on the amount of alcohol ingested, when it was consumed during the pregnancy, and whether drinking occurred in binges. No one has yet identified a safe drinking level; even moderate or occasional drinking may place the fetus at some risk. Until more is known, most doctors recommend that pregnant women abstain from drinking alcohol, especially during the early months of pregnancy.

Currently, there is no concrete evidence that marijuana or heroin cause fetal malformations. Cocaine and methamphetamine use during pregnancy, however, have been associated with shortened limbs and intestinal malformations, presumably because of constriction of fetal blood vessels. Heroin or methadone use by a pregnant woman may lead to a serious physical withdrawal state in the baby during the first week of life, characterized by episodes of hypoglycemia (low blood sugar) and seizures. Cigarette smoking has not been proven to cause fetal malformations but is associated with an increased occurrence of prematurity and low birth weight.

Multifactorial Conditions

In addition to purely genetic or environmental causes, sometimes interactions occur between heredity and the environment, as in cleft palate and in spina bifida. These are called multifactorial conditions. In spina bifida, an insufficient intake of the vitamin folic acid (an environmen-tal factor) places certain susceptible women (a genetic factor) at an increased risk for bearing children with a birth defect of the spine. Even teratogenic effects of medications can be related to a genetic influence. The antiepileptic drug Dilantin (phenytoin) has been found to have a much greater likelihood of causing malformation in fetuses of women who have a genetically based deficiency of an enzyme that breaks down this drug.

Viral Infections

Illness in a pregnant woman, especially certain viral infections, can also affect the fetus, causing brain damage and related disabilities. Traditionally the acronym TORCH has been used to denote the most common such infections: toxoplasmosis, other infections (including varicella, also known as chicken-pox), rubella, cytomegalovirus (CMV), and herpes. In the past, the most common virus causing fetal damage was rubella, or German measles. This illness causes only a low-grade fever and rash in the mother but can severely affect the fetus. Approximately one half of mothers infected with rubella during the first 3 months of pregnancy bear babies who have visual impairment, deafness, and usually mental retardation. Until 1969, when a rubella vaccine became available, epidemics occurred at 8-year intervals. Since that time, fetal rubella syndrome, which affects infants whose mothers had rubella during pregnancy, has become very rare. Women are now routinely given a blood test before they become pregnant to determine whether they have antibodies against rubella. If they do not, they are vaccinated and told to avoid becoming pregnant for 2 months. Even women who have become pregnant within several weeks of their vaccination have had unaffected babies. Now the most commonly occurring prenatal infections are toxoplasmosis, CMV, herpes, and HIV (human immunodeficiency virus). Although there are no commonly used vaccines for these disorders, certain treatments can decrease the risk of fetal damage in some of these infections.

Toxoplasmosis is a rare illness, most commonly passed from cat to human, that can cause microcephaly (small head size), blindness, deafness, and mental retardation in 40% of children born to infected mothers. Treating the infected mother early in pregnancy with Rovamycina (spiramycin), Daraprim (pyrimethamine), sulfadiazine, and Leucovorin (folinic acid) has been shown to improve the long-term outcome for the fetus.

Chickenpox infection in the mother may also harm the fetus during the first 3 months of pregnancy, although the abnormalities are less severe and less common than they are with rubella, CMV, toxoplasmosis, or herpes. Limb or facial abnormalities and, less frequently, brain damage may result. A vaccine for chickenpox is now available but is not commonly used in adults. CMV infections often do not cause symptoms in the mother but may cause malformations and mental retardation in the fetus. Some research sug-gests that 10% of all babies with microcephaly may have been affected by CMV infection of the mother during early pregnancy. Later in pregnancy, CMV infection may cause progressive hearing loss but not mental retarda-tion in the fetus. Only a small fraction of fetuses exposed to CMV (perhaps 1 in 100) develop abnormalities. The high incidence of this infection in the general population has led to the development of a vaccine that currently is undergoing testing.

The herpes simplex virus can infect the baby before birth only if the mother develops a severe infection with a high fever and a rash. Cold sores and vaginal infections do not affect the development of the fetus. A baby born to a mother with vaginal herpes, however, is at significant risk for contracting herpes while passing through the birth canal. A generalized infection in the newborn can be life threatening and can cause mental retardation. Infants of mothers with vaginal herpes are delivered by C-section (cesarean section) to decrease their risk of infection.

The most recent concern for fetal infection is HIV, the cause of AIDS (acquired immunodeficiency syndrome). AIDS damages the body's immune system, leaving the affected individual at the mercy of infections. HIV/AIDS is primarily transmitted through unprotected sexual intercourse or through contact with HIV/AIDS-infected blood. Women who become pregnant while carrying HIV can pass it to their babies, usually around birth. Because the fetal infection begins late in gestation, it does not cause malformations but places the child at risk for developing AIDS during early childhood. The use of Zidovudine (ZDV, or AZT) therapy in combination with C-section delivery has been found to decrease the risk of mother-infant transmission. Breastfeeding is also discouraged.

Maternal Illness

Unlike the specific viral infections just mentioned, other acute viral and bac-terial infections such as influenza, strep throat, and urinary tract infections do not damage the fetus. Thus, pregnant women shouldn't worry if they have a cold or fever during pregnancy and should also remember that after the first 3 months of pregnancy, malformations are unlikely to occur because the fetus's major body organs have already been formed. Research suggests, however, that in utero infections later in pregnancy may predispose the fetus to develop cerebral palsy.

In addition, certain chronic maternal illnesses place the fetus at risk. The most common of these are diabetes and seizure disorders. Fetuses of mothers with diabetes are at risk for a number of abnormalities, including spina bifida, heart problems, and malformations of the legs. Later in pregnancy there is an increased risk of toxemia (described in the next section) and premature birth. Good control of blood sugar levels appears to protect the fetus partially. At birth the infant of a mother with diabetes is likely to require treatment for hypoglycemia. With expectant mothers who have seizure disorders, the drugs used to treat the seizures rather than the seizures themselves appear to cause fetal malformations. Cessation of antiepileptic medication during the first trimester prevents malformations in infants born to these women. The risk to the fetus, however, must be balanced against the potential risk of uncontrolled seizures to the mother.

Other chronic illnesses do not cause malformations but do result in an increased risk of toxemia, prematurity, or growth retardation in the fetus. These conditions include maternal hypertension (high blood pressure) and rheumatologic disorders (rheumatoid arthritis, lupus, and so forth). As in diabetes, if the disease is managed well or is in remission, the outcome for the fetus is usually good. The drugs used to treat these diseases (other than methotrexate, used for rheumatologic disorders) are not teratogens.