Birth defects

• Birth defects can cause disabilities and even death.
• Alcohol and drug use while pregnant can cause birth defects.
• Ask your provider what you can do to prevent birth defects.

About 120,000 babies (1 in 33) in the United States are born each year with birth defects (1). A birth defect is an abnormality of structure, function or metabolism (body chemistry) present at birth that results in physical or mental disabilities or death. Thousands of different birth defects have been identified (2). Birth defects are the leading cause of death in the first year of life (3).

What causes birth defects?
Genetic and environmental factors, or a combination of these factors, can cause birth defects. However, the causes of about 70 percent of birth defects are unknown (1).

How are genetic disorders passed on to the child?
There are three main categories of genetic birth defects:

1. Single-gene defects: A mutation (change) in a single gene can cause birth defects. Every human being has about 20,000 to 25,000 genes that determine traits like eye and hair color (4). Genes also direct the growth, development and functioning of every system in the body. Genes are packaged into each of the 46 chromosomes inside our cells.
   
   A child gets half its genes from each parent. A person can inherit a genetic disease when one parent (who may or may not have the disease) passes along a single faulty gene. This is called dominant inheritance. Each child of a parent with the gene has a 50-percent chance of inheriting the disorder. Examples include:
   
   
   • Achondroplasia (a form of dwarfism)
   • Marfan syndrome (a connective-tissue disease)
   
   Other genetic diseases are inherited when both parents (who do not have the disease) carry an abnormality in the same gene and pass it on to a child. This is called recessive inheritance. Each child of two parents who have the abnormal gene has a 25-percent chance of inheriting the disorder. Examples include:
   
   
   • Tay-Sachs disease (a fatal nervous system disorder)
   • Cystic fibrosis (a serious disorder of lungs and other organs, affecting mainly caucasians)
   
   X-linked is another form of inheritance in which sons can inherit a genetic disease from a mother who carries an abnormal gene (usually with no effect on her own health). Each son of a mother who carries an abnormal gene has a 50 percent chance of inheriting the disorder. Daughters usually do not inherit the disorder, but they may be carriers like their mother. Examples include:
   
   
   • Hemophilia (a blood-clotting disorder)
   • Duchenne muscular dystrophy (progressive muscle weakness)
2. Chromosomal birth defects: Abnormalities in the number or structure of chromosomes can cause many birth defects. Chromosomal abnormalities usually are caused by an error that occurred when an egg or sperm cell was developing. Because of the error, a baby can be born with too many or too few chromosomes, or with one or more chromosomes that are broken or rearranged. Examples include:
   
   
   • Down syndrome (an extra copy of chromosome 21 or other rearrangements resulting in extra genetic material from this chromosome): Affected children have varying degrees of intellectual disabilities, characteristic facial features and, often, heart defects and other problems.
   • Trisomies 18 and 13 (an extra copy of chromosome 18 or 13): Affected babies have multiple birth defects and often die in the first months of life.
   • Sex chromosome abnormalities (missing or extra copies of the sex chromosomes, X and Y): These disorders affect sexual development and may cause infertility, growth abnormalities and behavioral and learning problems. However, most affected individuals live fairly normal lives. Examples include Turner syndrome (in which a girl is missing all or part of an X chromosome) and Klinefelter syndrome (in which a boy has one or more extra X chromosomes).
3. Multifactorial birth defects: Some birth defects appear to be caused by a combination of genes and environmental exposures. This is called multifactorial inheritance. In some cases, an individual may inherit one or more genes that make him more likely to have a birth defect if he is exposed to certain environmental substances, such as cigarette smoke. These individuals have a genetic predisposition to a birth defect. But if the individual is not exposed to the environmental substance before birth, he probably won’t have the birth defect. Examples of multi-factorial birth defects include:
   
   
   • Cleft lip/palate (opening in the lip and/or roof of the mouth)
   • Neural tube defects (NTDs) (serious birth defects of the brain and spinal cord, including spina bifida and anencephaly)
   • Heart defects

What environmental factors contribute to birth defects?
Environmental substances that can cause birth defects are called teratogens. These include alcohol, certain drugs/medications, infections and certain chemicals:

Alcohol: Each year between 1,000 and 6,000 babies in the United States are born with fetal alcohol syndrome (FAS) (5). FAS is a pattern of mental and physical birth defects that is common in babies of mothers who drink heavily during pregnancy. Women who are pregnant or planning pregnancy should not drink any alcohol. Even moderate or light drinking during pregnancy may harm the baby.

Drugs: Illegal drugs, including cocaine, marijuana and Ecstasy, may cause birth defects. Pregnant women should not take illegal drugs and should tell their providers if they need help to quit. Some prescription drugs also can cause birth defects. A woman taking any of the following prescription drugs should talk to her provider before getting pregnant. She may need to switch to a safer drug for pregnancy:

• ACE inhibitors (enalapril or captopril)
• Androgens and testosterone by-products
• Anticancer drugs
• Antifolic acid drugs, like methotrexate or aminopterin
• Carbamazepine
• Levothyroxine
• Lithium
• Phenytoin
• Streptomycin and kanamycin
• Tetracycline
• Trimethadione and paramethadione
• Valproic acid
• Warfarin and other coumarin by-products

If a woman is pregnant and taking any of the following drugs, she should stop taking the medicine immediately and call her health care provider:

• Acccutane, Amnesteem, Claravis, Sotret (isotretinoin) and other retinoids
• Soriatane (acitretin)
• Thalomid (thalidomide)
• Revlimid (lenalidomide)

A woman who is pregnant or thinking about getting pregnant should tell her provider about any drugs she takes to make sure they are safe for pregnancy.

Infections: Certain infections can cause birth defects when a woman gets them during pregnancy. About 30,000 babies a year (about 1 in 150 newborns) in this country are born with a viral infection called cytomegalovirus (CMV) (6). About 8,000 infected babies each year develop permanent disabilities, including intellectual disabilities and loss of vision and hearing (6). Pregnant women often get CMV from young children who have few or no symptoms.

Sexually transmitted infections (STIs): STIs in the mother can endanger the fetus and newborn. For example, untreated syphilis can cause stillbirth, newborn death or bone defects. About 350 babies were affected by congenital syphilis in the United States in 2006 (7).

Chemicals: Little information is known about the effects of most chemicals during pregnancy. However, a small number of chemicals are known to be harmful to an unborn baby. Most of these are found in the workplace. For example, workplace exposure to organic solvents (chemicals that dissolve other substances), such as alcohols, degreasers, paint thinners and varnish removers, are suspected of increasing the risk of birth defects. High levels of exposure to pesticides, on the job or at home, also may contribute to birth defects and other pregnancy complications. Pregnant women should avoid pesticides whenever possible, and those who work with chemicals should follow all preventive measures to reduce their exposure. A woman who is pregnant or planning pregnancy should also discuss all workplace chemical exposures with her health care provider to see if additional on-the-job protections are advisable.

What are the most common birth defects?
Some of the most common birth defects include:

• Heart defects: As many as 1 in 100 babies in the United States are born with heart defects each year (1). While advances in surgery have dramatically improved the outlook for affected babies, heart defects remain the leading cause of birth defect-related infant deaths (8).
• Cleft lip/palate: About 1 in 700 babies is born with cleft lip/palate each year (1). Affected babies can have problems with eating, speech and language. Some have a small cleft that can be corrected with one surgical procedure, while others have severe clefts and need multiple surgeries.
• Down syndrome: This chromosomal abnormality affects about 1 in 800 babies in the United States (1). Early intervention programs and treatment of associated health problems have greatly improved the outlook for affected individuals.
• Spina bifida (open spine): This disorder affects about 1 in 2,500 babies in the United States each year (1). Affected babies have varying degrees of paralysis and bladder and bowel problems.

Other common birth defects include musculoskeletal defects (including arm and leg defects), gastrointestinal defects (including defects of the esophagus, stomach and intestines) and eye defects. These birth defects usually are multi-factorial.

What are birth defects of body chemistry?
In 2004, about 4,000 babies in the United States were born with disorders affecting body chemistry (9). These are called metabolic disorders. Most metabolic disorders are recessive genetic diseases. These disorders are not visible, but they can be harmful or even fatal. Many metabolic disorders can be routinely detected with newborn screening tests, allowing early treatment and healthy development. The March of Dimes recommends that all newborns be screened for 30 disorders (including hearing loss) for which effective treatment is available. Examples of the 30 disorders include:

• Phenylketonuria (PKU): Affected babies cannot process a part of protein, which builds up and damages the brain. Affected babies are placed on a special eating plan that prevents intellectual disabilities. Affected individuals generally should follow a special eating plan throughout life.
• Galactosemia: Affected babies cannot process galactose (a sugar in milk), which builds up and can lead to intellectual disabilities, blindness and death. Affected individuals are treated with a special eating plan free of dairy products.

Some metabolic disorders cannot yet be treated. An example is Tay-Sachs disease. Affected babies lack an enzyme needed to break down certain fatty substances in brain cells. These substances build up and destroy brain cells, resulting in blindness, paralysis and death by age 5.

Can birth defects be prevented?
There are a number of steps a woman can take before and during pregnancy to reduce her risk of having a baby with a birth defect:

• Get a preconception checkup with a health care provider. This is a medical checkup a woman gets before getting pregnant. During this visit, the provider can identify and often treat health conditions that can pose a risk in pregnancy. A preconception visit is especially crucial for women with chronic health conditions, like diabetes, high blood pressure and epilepsy, that can affect pregnancy. For example, women with diabetes who have poor blood-sugar control are several times more likely than women without diabetes to have a baby with a serious birth defect. However, if their blood sugar levels are well controlled before pregnancy, they are almost as likely to have a healthy baby as women without diabetes (10).
• Make sure her vaccinations are up-to-date. All women should be tested for immunity to rubella (German measles) and chickenpox before getting pregnant and consider being vaccinated if they are not immune. After being vaccinated, a woman should wait 1 month before becoming pregnant. Rubella poses a high risk of birth defects if a woman gets infected during pregnancy. Chickenpox also can cause birth defects, though the risk is low.
• Take a multivitamin containing 400 micrograms of folic acid daily starting before pregnancy and in early pregnancy to help prevent NTDs. If a woman already has had a pregnancy affected by an NTD, she should consult her provider before pregnancy about how much folic acid to take. Generally a higher dose, 4 milligrams, is recommended (11). Women with diabetes or epilepsy or who are obese are at increased risk of having a baby with these birth defects. They should ask their providers before pregnancy about whether they should take the larger dose of folic acid.
• Eat healthy foods, including foods containing folic acid and folate, the form of folic acid that occurs naturally in foods. Foods high in folic acid include fortified breakfast cereals, enriched grain products, beans, leafy green vegetables and orange juice.
• Get early and regular prenatal care.
• Don’t eat undercooked meat or change a cat’s litter box. Both are possible sources of toxoplasmosis, an infection that can cause birth defects.
• Avoid contact with all rodents, including hamsters, mice and guinea pigs. These animals can carry a virus that can harm a baby.
• Don’t eat fish that contain high amounts of mercury. These fish include shark, swordfish, king mackerel or tilefish. It’s all right for a pregnant woman to eat up to 12 ounces a week of fish that have small amounts of mercury, such as shrimp, salmon, pollock, catfish and canned light tuna. But she should not eat more than 6 ounces of albacore (white) tuna per week. Women also should check local advisories about the safety of fish caught in local waters.
• Begin pregnancy at a healthy weight (not too heavy or too thin).
• Don’t smoke and avoid secondhand smoke.
• Don’t drink alcohol.
• Don’t use any drug, even over-the-counter medications or herbal preparations, unless recommended by a health care provider who knows the woman is pregnant.

Can some birth defects be diagnosed before birth?
Providers can diagnose some birth defects before birth using one or more prenatal tests, including ultrasound, amniocentesis and chorionic villus sampling (CVS). Ultrasound can help diagnose structural birth defects, such as spina bifida, heart defects and some urinary tract defects. Amniocentesis and CVS are used to diagnose or rule out chromosomal abnormalities, such as Down syndrome and many genetic birth defects. Most women have screening tests (blood tests) to see if they are at increased risk of certain birth defects, including Down syndrome and spina bifida. These screening tests cannot diagnose a condition, but they can suggest that further diagnostic testing is needed.

Can birth defects be treated before birth?
A small percentage of couples learn through prenatal diagnosis that their baby has a birth defect. While this news can be devastating, prenatal diagnosis sometimes can improve the outlook for the baby. It is now possible to treat some birth defects before birth. For example, biotin dependence and methylmalonic academia, two life-threatening inherited metabolic disorders, have been diagnosed by amniocentesis and treated in the womb, resulting in the births of healthy babies.

Prenatal surgery has saved babies with urinary tract blockages and rare lung tumors. However, prenatal surgery poses a number of serious risks for mother and baby, including preterm birth. The National Institutes of Health is conducting a study to compare the safety and effectiveness of surgery before and after birth for babies with spina bifida. For information, contact spinabifidamoms.com. Doctors also have saved babies with serious heart-rhythm disturbances by treating the pregnant woman with medications.

Even when a fetus has a condition for which prenatal treatment is not yet possible, prenatal diagnosis permits parents to prepare themselves emotionally and to plan with their provider the safest timing, hospital facility and method of delivery.

Couples who have had a baby with a birth defect or who have a family history of birth defects should consider consulting a genetic counselor. These health professionals help families understand what is known about the causes of a birth defect and the chances of the birth defect recurring in another pregnancy. Genetic counselors can provide referrals to medical experts as well as to appropriate support groups in the community. Genetic counseling is available at most large medical centers and teaching hospitals. To find a genetic counselor in their area, individuals can ask their health care provider or visit the National Society of Genetic Counselors.

References

1. Centers for Disease Control and Prevention (CDC). Birth Defects. Retrieved March 11, 2009.
2. National Institutes of Health (NIH). Birth Defects. Retrieved May 11, 2009.
3. Mathews, T.J. and MacDorman, M.F. Infant Mortality Statistics from the 2005 Period Linked Birth/Infant Death Data Set. National Vital Statistics Reports, volume 57, number 2, July 30, 2008.
4. National Human Genome Research Institute. A Brief Guide to Genomics. Retrieved December 23, 2008.
5. Centers for Disease Control and Prevention (CDC). Erratum: Volume 54, No. RR-11. Morbidity and Mortality Weekly Report, volume 55, number 20, May 26, 2006, page 568.
6. Centers for Disease Control and Prevention (CDC). Cytomegalovirus. Retrieved November 3, 2008.
7. Centers for Disease Control and Prevention (CDC). Syphilis – CDC Fact Sheet. Updated 1/4/08.
8. Kung, H., et al. Deaths: Final Data for 2005. National Vital Statistics Report, volume 56, number 10, April 24, 2008.
9. Overview of NBS Programs: States of the States. Briefing Presented at the First Meeting of the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children, June 7-8, 2004, Washington, DC.
10. American College of Obstetricians and Gynecologists (ACOG). Pregestational Diabetes Mellitus. ACOG Practice Bulletin, number 60, March 2005 (reaffirmed 2007).
11. Centers for Disease Control and Prevention (CDC). Folic Acid: Questions and Answers. Updated March 31, 2009.

June 2009, April 2010, June 2010