Cystic Fibrosis Screening -Infant

Cystic Fibrosis Screening -Infant

Cystic Fibrosis Screening

Summary of Recommendation and Evidence

Population

Recommendation

Grade
(What's This?)

Screening of both Genders

The genetic screening for Cystic Fibrosis is recommended.

B

Cystic fibrosis is a genetic disorder that often affects multiple organ systems of the body. Cystic fibrosis is characterized by abnormalities affecting certain glands (exocrine) of the body especially those that produce mucus. Saliva and sweat glands may also be affected. 

OVERVIEW

CF occurs when a patient carries two deleterious mutations for cystic fibrosis transmembrane conductance regulator (CFTR) function. CFTR mutations result in impaired chloride ion channel function and abnormal secretions in sweat glands, lungs, liver, pancreas, digestive system, sinuses, and reproductive system. This accumulation of thick and sticky secretions results in decreased organ function, especially in the lungs, and makes patients prone to pulmonary infections. In addition, individuals with CF may have difficulty absorbing nutrients, causing malnutrition and fatty stools. With recent advancements in care, individuals with CF are living longer – current life expectancy is greater than 37 years.

SCREENING

Finding

All 50 states screen newborns for cystic fibrosis (CF), though the method of testing varies. Trypsinogen, which is produced only in the pancreas, is elevated in infants with CF and is tested for by an immunoassay (immunoreactive trypsinogen or IRT). State programs react to a high IRT screening level in several ways: some go directly to genetic testing, some repeat the IRT and, if both tests are abnormal, notify the primary care physician (PCP), some repeat the IRT and then send the blood spot for genetic testing and, if genetic testing shows one of the CFTR mutations, then notify the PCP and family. All positive testing on the newborn screen, whatever the method, should be followed by sweat chloride testing, the gold standard for diagnosis. Infants born, or presenting in the first few days of life, with meconium ileus due to CF may have normal trypsinogen levels and would therefore not test positive on newborn screening. Infants with meconium ileus are tested directly with DNA and sweat chloride testing.

Tested By

Immunoassay for trypsinogen (immunoreactive trypsinogen test, or IRT); followed by repeat testing and/or CFTR mutation analysis, depending on the state.

PREVALENCE

CF is the most common life-threatening autosomal recessive disease in the United States, occurring in approximately 1:3500 newborns. 

INHERITANCE

CF is inherited in an autosomal recessive manner. It affects both boys and girls equally.

MATERNAL & FAMILY HISTORY

Maternal carrier genetic testing is offered to women of child-bearing age.

PRENATAL TESTING

DNA testing of samples obtained by amniocentesis or chorionic villus sampling (CVS) is available; most screens look for 30+ mutations, although over 1500 known mutations are known to cause CF. If there is a family history of CF, prenatal testing should include known family mutations.

OTHER TESTING

Sweat testing is performed when there is meconium ileus or a positive newborn screen. Because newborn screening genetic testing looks for only a small number of disease-causing mutations, sweat chloride testing should be performed if a child is symptomatic, regardless of the screening results. Additional and more detailed genetic testing may be needed for positive or borderline sweat test results. The CF Foundation certifies only a limited number of sweat chloride testing sites. Other institutions may utilize sweat conductivity which is a screening test, not a diagnostic test.

CLINICAL CHARACTERISTICS

With treatment, health complications are reduced and survival into middle adulthood is common. The CF Foundation has established care centers, certified sweat chloride testing, advocated for CF newborn screening, and more, all of which have helped survival in children with CF. Without treatment, symptoms may vary. With more severe CFTR mutations, acute and chronic respiratory infections, chronic digestive complications, diabetes, and other symptoms can be expected. Children with two severe mutations generally have malabsorption in the newborn to early childhood period. One mild mutation in conjunction with a severe mutation often results in pancreatic sufficiency. These patients may not need pancreatic enzyme supplementation. The presentation of CF-related lung disease cannot always be predicted by the severity of the CFTR mutation.

Initial symptoms may include:

  • Meconium ileus
  • Salty sweat or sweat crystals on the skin
  • Poor weight gain
  • Smelly, greasy, bulky, and bright green stools (even in breast fed infants)
  • Diarrhea, constipation, or persistent abdominal pain
  • Rectal prolapse
  • Persistent coughing or wheezing
  • Thick phlegm and mucus
  • Recurrent lung and sinus infections
  • Nasal polyps

 

If not treated, patients may experience:

  • Malnutrition and poor growth
  • Electrolyte depletion
  • Pulmonary damage or bronchiectasis
  • Diabetes
  • Pancreatitis
  • Liver disease
  • Death in childhood

EARLY SIGNS

Signs of cystic fibrosis (CF) usually start shortly after birth. Some signs may not appear right away. This is why identification through newborn screening is so important.

Early signs of CF include:

  • Salty sweat; many parents notice a salty taste when kissing their child
  • Poor growth and weight gain (failure to thrive)
  • Constant coughing and wheezing
  • Thick mucus or phlegm
  • Greasy, smelly stools that are bulky and pale colored

If your baby shows any of these signs, be sure to contact your baby’s doctor immediately.

CAUSES

In our bodies, particles called chloride ions help control the movement of water. This allows the different parts of our body to make an adequate supply of thin, freely flowing mucus. Mucus helps protect the body from dirt, bacteria, and viruses that can be inhaled.

Individuals with cystic fibrosis (CF) are unable to move chloride ions and water throughout their body. As a result, the lungs, pancreas, and other organs produce mucus that is unusually thick and sticky. This mucus is unable to protect the body. Therefore, mucus clogs the body's airways and glads and reduces its ability to fight infections. 

CF is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for CF, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with CF is rare, when both parents are carriers, they can have more than one child with the condition.

TREATMENT

Dietary Treatment and Supplements
  • A high-calorie diet – Some children with cystic fibrosis (CF) need more food for healthy growth and development.
  • Pancreatic enzymes – Your baby may need to take pancreatic enzymes before eating to properly digest food. These enzymes can help your baby gain weight and grow at a healthy rate.
  • Vitamin supplements – Your baby’s body may also have trouble getting vitamins from food. Your baby’s doctor may prescribe vitamin supplements to ensure proper nutrition.
Medications

Some children need special medications to treat the lung problems associated with CF. Your baby’s doctor may prescribe one or more of the following:

  • Mucus-thinners – These drugs are usually inhaled, and they help make mucus thinner and easier to cough up.
  • Bronchodilators – These inhaled drugs open up the airway to make breathing easier.
  • Anti-inflammatories – These drugs can help reduce lung swelling.
  • Antibiotics – Children with CF tend to have frequent lung infections, which may require treatment with antibiotics.
Airway Clearance Therapy (ACT)

Airway Clearance Therapies (ACT) are treatments that help people with CF loosen thick, sticky lung mucus so that it can be cleared by coughing. This will help your child stay healthy and breathe more easily. There are a number of ways to perform ACT. Your baby’s doctor will help you choose the most effective technique for your baby.

EXPECTED OUTCOMES

At this time, the goal of treatment for cystic fibrosis (CF) is to minimize the signs and symptoms of the condition. There is currently no cure available for CF. Although CF is a life-shortening condition, early identification and lifelong management allow many people with CF to live longer than ever before.

Over time, children with CF often have chronic coughing and wheezing, repeat lung infections which can lead to permanent lung damage, digestive problems, poor growth and weight gain, malnutrition, and infertility (most common in males).

Even with early identification, some adults with CF may develop severe lung damage, which can no longer be treated with medications. In this case, a doctor may recommend a lung transplant. Without treatment, children with CF are at risk of early death. This is why newborn screening for CF is so important.