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.

Cystic fibrosis (CF) is an inherited disease that affects the lungs and digestive system. Advances in medical treatment have improved the outlook for affected children and adults. Most affected individuals survive into their late 30s, though some die in childhood and others live to age 40 or beyond (1). There is currently no cure.

The abnormal gene that causes CF was discovered in 1989. Since then scientists have found more than 1,500 mutations (changes) in the gene that lead to CF (2). A test called a carrier screening test checks for the most common of these mutations to help determine whether a couple is at increased risk of having a baby with CF. A new test can now detect 39 of these mutations (the March of Dimes does not endorse specific brands or products).

The test is routinely offered to couples who have a family history of CF. Many health care providers also make this test available to couples who are planning pregnancy or are pregnant. Couples must decide for themselves if testing is right for them.

What is cystic fibrosis?
CF is an inherited disease that affects the normal movement of salt (sodium chloride) and water into and out of certain cells, including those that line the lungs and pancreas. This results in thick, sticky mucus and other secretions.

The mucus clogs the lungs, causing breathing problems. The build-up of mucus in the lungs also provides a breeding ground for bacteria to grow. This leads to frequent lung infections, which eventually damage the lungs and contribute to early death.

Thick, digestive fluids may clog ducts leading from the pancreas to the small intestine. This prevents digestive enzymes from reaching the small intestine, where they are needed to break down and absorb food. This can cause digestive problems, slow growth and malnutrition.

How common is CF?
CF is one of the most common, life-threatening genetic diseases in the United States. It affects all racial and ethnic groups; however, it is most common among caucasians. About 1 in 3,500 babies are born with CF (2), which affects about 30,000 children and adults in the United States (1, 3).

What are the symptoms of CF?
The symptoms of CF vary and can range from mild to severe. Some common symptoms include:

• Coughing or wheezing
• Excessive mucus in the lungs
• Frequent lung infections, such as pneumonia and bronchitis
• Shortness of breath
• Salty-tasting skin
• Poor growth, despite a big appetite
• Intestinal blockage, called meconium ileus, in a newborn (caused by thickening of the greenish stool newborns usually pass in the first days of life)
• Greasy, bulky stools
• Small, fleshy growths in the nose called nasal polyps
• Clubbing (enlargement) of the fingertips and toes
• Infertility in affected males due to blockage or absence of the tube (vas deferens) that carries sperm out of the testicles

Many lung infections in individuals with CF are caused by a bacterium called Pseudomonas aeruginosa. This bacterium rarely causes problems in people who do not have CF. Antibiotics often cannot completely clear this bacterium from the lungs. These infections contribute to lung damage.

Most children with CF are well enough to exercise and attend school. Health care providers recommend exercise in individuals with CF because it helps loosen mucus in the lungs and strengthens the heart and lungs.

How is CF diagnosed?
Most states now routinely screen all newborns for CF, along with other inherited disorders (4). With newborn screening, infants with CF are usually diagnosed in the first 2 months of life. The newborn screening test does not actually diagnose CF. Infants with abnormal results on their newborn screening test receive follow-up diagnostic tests, including a sweat test and, sometimes, a gene test using a blood sample or saliva. The new CF gene test used to detect carriers can also be used to detect more mutations in newborns with abnormal screening test results.

The sweat test is a simple, painless test that measures the amount of salt in the sweat. Individuals with CF have more salt in their sweat than unaffected individuals. In some cases, the health care provider may recommend a gene test to confirm the diagnosis. Both the sweat test and the gene test are accurate in diagnosing CF. However, they do not predict how severe the child’s symptoms will be. These tests also are used to diagnose CF in older children and adults.

On further testing, most infants with abnormal CF screening test results are found not to have CF. However, newborn screening can improve the outlook for infants with CF. Early diagnosis leads to faster treatment, which improves growth and lung function and reduces the risk of serious complications and early death (5, 6, 7).

Children who are not diagnosed with CF through newborn screening are diagnosed when they begin to develop symptoms. About 15 percent of newborns with CF have meconium ileus (intestinal blockage) (7). These infants are diagnosed and treated in the first months of life. Most others are diagnosed in the first few years of life when they develop repeated lung infections or grow poorly.

How are lung problems prevented and treated in individuals with CF?
Children and adults with CF need close medical supervision throughout their lives.

Many individuals with CF need daily respiratory therapy. This is done at home at least once and sometimes four or more times a day (1). There are a number of airway clearance techniques that can help loosen and clear mucus from the lungs. For example:

• Parents or other caretakers clap the child on the back and chest with their hand or with an electric chest clapper.
• The person with CF uses an inflatable vest that vibrates or a flutter, a handheld device that vibrates the airways as the person exhales. Then the individual coughs or huffs (an active form of exhaling) to clear the mucus.

The individual’s health care team can recommend the most effective approach.

A number of medications can help individuals with CF breathe better and prevent infections. Some come in a mist form that the individual inhales into the lungs. The provider recommends different medications depending on the person’s symptoms and how severe they are. Types of medications include (1, 8):

• Mucus-thinners: Drugs such as Pulmozyme (Dnase) help thin mucus, making it easier to cough out.
• Bronchodilators: These medications help clear mucus and keep airways open. Examples are Albuterol, Proventil and Ventolin.
• Antibiotics: These medications prevent and treat infections. An inhaled antibiotic called TOBI (tobramycin) is commonly used, as is an oral antibiotic called azithromycin.
• Ibuprofen: This oral, non-steroidal, anti-inflammatory drug may help reduce lung inflammation (redness and swelling) that can make breathing difficult.
• Hypertonic saline: Inhaling a sterile salt-water mist helps draw more water into the airways, which helps thin the mucus

In spite of these treatments, infections occur. Infections may be treated at home or in the hospital with a number of antibiotics, which can be given by mouth, through a vein (intravenously) or by inhalation.

Unfortunately, as the individual gets older, infections tend to get worse and more difficult to treat, often leading to serious lung damage. Infection, and the resultant lung damage, is the leading cause of death in individuals with CF.

Lung transplantation is an option for some individuals who develop life-threatening lung complications and have exhausted all other treatment options. This is a major operation, but it is becoming increasingly successful in improving symptoms in some severely affected individuals (1).

How are growth and digestive problems prevented and treated?
Some infants and children with CF gain weight and grow normally, but many grow more slowly than unaffected children. This is because sticky mucus blocks pancreatic enzymes from reaching the small intestine, where most digestion and absorption of nutrients takes place. As a result, affected children may absorb fewer calories and nutrients, leading to slow growth.

Many individuals with CF experience symptoms related to poor digestion. These include (1):

• Slow weight gain, despite a good appetite
• Frequent, loose or large bowel movements
• Bowel movements that contain mucus or oil
• Gas, stomach pain and bloating

Most individuals with CF need to take medications containing pancreatic enzymes with each meal. These enzymes help the body absorb nutrients from food, improving weight gain and digestive symptoms. To improve growth, children with CF must eat healthy, high-calorie foods supplemented with certain vitamins (especially vitamins A, D, E and K) (1). A dietitian who is experienced with CF can help a family plan a child’s meals to achieve a healthy weight gain.

About 40 percent of adults with CF develop a CF-related form of diabetes, which is usually treated with insulin injections at meal times (1). It is important to keep diabetes under control because poorly controlled diabetes can contribute to worsening lung function (1).

Can a person catch CF from someone who has it?
No. The disease is inherited and is not contagious.

How is CF inherited?
Genes come in pairs. To inherit CF, a child must receive two abnormal CF genes, one from each parent who “carries” an abnormal CF gene. A carrier is a healthy individual who has one normal CF gene and one abnormal CF gene in the pair.

When both parents carry an abnormal CF gene, there is a 25 percent (1 in 4) chance that the child will have CF. There is a 50 percent chance (1 in 2) that the child will be a carrier like the parents. There also is a 25 percent chance that the child will be free of the abnormal gene and neither be a carrier, nor have the disease.

The couple has the same risks with each pregnancy. If only one parent is a carrier, there is no chance that their children will have CF.

Who should have the carrier screening test?
The American College of Obstetricians and Gynecologists (ACOG) recommends that the carrier screening test be available to all couples who are planning pregnancy or are pregnant (9). Many health care providers give couples printed material to read about the test. Those who are interested in testing can then discuss it further with their provider.

Health care providers often offer the test to couples considered at increased risk of having an affected child. At-risk couples include caucasians and couples with a family history of CF.

A couple must decide for themselves whether or not to take the carrier screening test. A couple must decide what is right for them after learning about CF and discussing the test with their health care provider.

How is the test done?
The health care provider takes a sample of blood or saliva. The sample is sent to a lab to test for the abnormal CF gene.

Who is most likely to be a carrier?
One in 31 Americans (more than 10 million people) carry an abnormal CF gene (1, 3). Someone with a family history of CF is more likely to carry an abnormal CF gene than someone from an unaffected family.

The risk of carrying the abnormal gene by ethnicity is as follows (1, 9):

• Caucasians: a 1 in 29 chance
• Hispanics: 1 in 46
• African-Americans: 1 in 65
• Asian-Americans: 1 in 90

What happens if the test shows that a woman is a carrier?
The next step is to test her partner. A baby is not at risk of CF unless both parents carry an abnormal CF gene. Fortunately, this situation is fairly uncommon. For caucasians, the chance that both partners carry an abnormal CF gene is about 1 in 800; the risk is less in other groups (9).

However, the carrier screening test is not 100 percent accurate. The test looks only for some of the most common CF mutations, so even when the test shows that a person is not a carrier, there’s a very small chance that he or she carries an abnormal gene.

What happens if both parents are carriers?
A couple in which both partners are carriers should consider consulting a genetic counselor. A genetic counselor can discuss the risks to their future children and the option of prenatal testing (using amniocentesis or chorionic villus sampling, also called CVS) to diagnose or rule out CF in a fetus.

Each child of parents who both carry an abnormal CF gene has a 25 percent (1 out of 4) chance of inheriting CF. This means that the child has a 75 percent (3 out of 4) chance of not inheriting CF.

When the fetus is affected, parents can take the time before delivery to learn more about the disease and locate appropriate specialists. Prenatal testing cannot, however, tell how seriously affected the baby may be.

Can women with CF become pregnant?
Some women with CF may have trouble getting pregnant, but many women with CF can get pregnant and have healthy pregnancies (10, 11, 12). Studies suggest that pregnancy does not shorten a woman’s survival (11).

Women with CF may be at increased risk of developing diabetes, which requires treatment both during and after pregnancy (11). Some women also may experience a slight decrease in lung function after pregnancy, possibly because new mothers may not follow their treatment regimens as closely as they did before pregnancy (11).

Women with CF who are considering pregnancy should consult their CF specialists before they become pregnant. They need continuing care throughout pregnancy from these specialists and from an obstetrician experienced with CF.

Babies of women with CF are not at risk of inheriting the disease unless the father carries the abnormal CF gene. When the woman is affected with CF, the couple should consult a genetic counselor and consider carrier screening for the partner before pregnancy.

Is the March of Dimes conducting research on CF?
March of Dimes research grantees are conducting studies aimed at improving the understanding of the basic cellular defects in CF as a basis for developing improved treatments.

• One grantee is seeking to learn how abnormalities in lung stem cells (unspecialized cells that produce other lung cells) contribute to lung damage in CF. The goal of this research is to develop drugs that could stimulate an individual’s own stem cells to repair lung damage.
• Another grantee is studying a gene that plays a role in lung growth to learn how to better promote lung growth following lung transplantation for CF.

Other researchers, not associated with the March of Dimes, continue to develop and test new drugs that aim to prevent or treat infections in those with CF, as well as drugs that may help correct the basic defect in lung cells.

What other sources of information on CF are available?
Information and referrals to local experts are available from the Cystic Fibrosis Foundation. The American Academy of Pedatrics also provides information on .


References

1. Cystic Fibrosis Foundation. About Cystic Fibrosis. Bethesda, MD, accessed 11/24/08.
2. Farrell, P.M. Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older Adults: Cystic Fibrosis Foundation Consensus Report. Journal of Pediatrics, volume 153, August 2008, pages s4-s14.
3. National Human Genome Research Institute. Learning About Cystic Fibrosis. Updated 4/10/08.
4. National Newborn Screening and Genetics Resource Center. National Newborn Screening Status Report. Updated 10/22/08.
5. Grosse, S.D., et al. Potential Impact of Newborn Screening for Cystic Fibrosis on Child Survival: A Systematic Review and Analysis. Journal of Pediatrics, volume 149, September 2006, pages 362-366.
6. Comeau, A.M., et al. Guideline for Implementation of Cystic Fibrosis Newborn Screening Programs: Cystic Fibrosis Foundation Workshop Report. Pediatrics, volume 119, number 2, February 2007, pages e495-e518.
7. Sims, E.J., et al. Cystic Fibrosis Diagnosed After 2 Months of Age Leads to Worse Outcomes and Requires More Therapy. Pediatrics, volume 119, number 1, January 2007, pages 19-28.
8. Flume, P.A., et al. Cystic Fibrosis Pulmonary Guidelines: Chronic Medications for Maintenance of Lung Health. American Journal of Respiratory Critical Care Medicine, volume 176, number 10, November 15, 2007, pages 957-969.
9. American College of Obstetricians and Gynecologists (ACOG). Cystic Fibrosis Testing: The Decision Is Yours. ACOG, Washington, DC, 2001.
10. Boyle, M.P. Adult Cystic Fibrosis. Journal of the American Medical Association, volume 298, number 15, October 17, 2007, pages 1787-1793.
11. McMullen, A.H., et al. Impact of Pregnancy on Women With Cystic Fibrosis. Chest, volume 129, number 3, March 2006, pages 706-711.
12. Gilljam, M., et al. Pregnancy in Cystic Fibrosis. Chest, volume 118, July 2000, pages 85-91.

March 2009/September 2009