During prenatal visits many parents ask me what is included in newborn screening tests. In particular African-American parents want to know if their child will be screened for sickle-cell disease since it runs in their family.

Sherri A. Zimmerman, MD, an associate professor of pediatrics, outlines the process for screening for sickle cell disease and some of the consequences and treatments for children who are diagnosed with sickle-trait or sickle-disease.

-- Dennis Clements, MD, PhD, MPH

Sickle cell disease (SCD) -- a group of inherited blood disorders -- affects one in every 375 African-American live births, but is also found in people of other ethnicities.

In sickle cell disease, a genetic mutation (change in the genes or chromosomes) leads to production of the sickle hemoglobin. Unlike normal adult hemoglobin (HbA), the sickle hemoglobin (HbS) can form polymers (long, rod-like structures) that lead to the sickle shape, rather than normal, round red blood cells.

Normal red blood cells

Sickled red blood cells

Normal red blood cells’ round shape helps them maneuver through small blood vessels to deliver oxygen to tissues.

When sickled cells form -- in response to low oxygen, for example -- they may get “stuck” in the small blood vessels and temporarily block blood flow and oxygen delivery to the tissues. This results in many of the clinical complications seen in sickle cell disease.

Newborn Screening

In many states, including North Carolina, all newborns are screened for sickle cell disease. Blood samples for newborn screening are collected as blood spots on filter paper shortly after birth.

This allows infants with sickle cell disease to be identified early so that their parents can be educated about the disease and the babies can begin treatment, which includes starting penicillin within two to three months of age.

Once children are identified as sickle cell disease or sickle cell trait, their parents are offered testing to confirm if they carry the sickle cell gene.

Other adults at high risk for carrying sickle cell trait should also be tested so that they can be educated about their risk for having a child affected with sickle cell disease. This would be performed by the adult’s physician.

Genetics of Sickle Cell Disease

Each parent has two alleles (parts of chromosomes) for hemoglobin and they pass one allele to each child. If each parent has a normal (A) allele and a sickle (S) allele then the possible combinations in their children are diagrammed below.

This means that for two adults with sickle cell trait, for each pregnancy there is:

• 25 percent chance of having a child with sickle cell anemia
• 25 percent chance of having a child with neither sickle cell trait nor SCD
• 50 percent risk of having a child with sickle cell trait

Patients with sickle cell trait usually show no symptoms and do not have the clinical complications seen in patients with sickle cell disease.

Health Complications

The clinical problems seen in children with sickle cell disease can affect almost any organ in the body.

Early in life, children with sickle cell disease are at increased risk for life threatening infections, especially with Streptococcus pneumoniae or “pneumococcus”. These infections can be prevented in most cases by prophylactic doses of penicillin given twice daily for the first three to five years of life.

In addition, routine childhood immunizations include the Prevnar, or PCV-7, vaccine helps to protect children against this potentially serious infection.

If children with sickle cell disease develop a fever of 101 degrees Fahrenheit or greater, it is essential that they are seen promptly for examination, blood work, and antibiotics (usually intravenous or by injection) until a potentially serious infection has been ruled out.

Other complications of sickle cell disease include:

• Lifelong anemia (low red blood count)
• Pneumonia (or acute chest syndrome)
• Painful vascular-occlusive events (sickle cells clump in arteries and cause vascular spasm and pain -- so-called “pain crises” or “hand-foot syndrome”)
• Stroke
• Enlargement of the spleen Kidney disease
• Eye problems (hemorrhages in the retina)
• Gallstones
• Bone damage due to reduced oxygen and then death of tissue in the hips or shoulder

For most complications of sickle cell disease, treatment involves giving fluids by vein, antibiotics for potential infection, pain medications (either by mouth or by vein), and sometimes blood transfusions for severe complications.

It is important that parents recognize signs and symptoms of these complications early and contact their pediatrician or sickle cell physician right away if they occur.

Get more information about each of these complications from the North Carolina Sickle Cell Syndrome Program.

Preventive Care

The care of children with sickle cell disease involves parents, community educators, primary care physicians, emergency room physicians, and pediatric hematologists with special expertise in sickle cell disease.

Over the last 10 to 15 years, there have been several important advances in the care of children with sickle cell disease -- particularly related to preventive care.

A simple, painless ultrasound test called transcranial doppler (TCD) has been shown to help identify children with sickle cell disease who are at highest risk of stroke. Stroke occurs in about 5 to 10 percent of children with sickle cell disease and can cause weakness, seizures, difficulty speaking, and problems in school performance. Once a child has a stroke, monthly blood transfusion therapy is started and continued for an indefinite period of time, typically years.

TCD screening is currently recommended for all children with sickle cell disease between two to 16 years of age.

Monthly blood transfusions have been shown to prevent children from having a first stroke and are indicated for those children at highest risk of stroke based on their TCD results.

Hydroxyurea (HU) therapy also offers the opportunity to prevent many of the clinical complications of SCD.

HU is a medication that can be given once daily to children and adults with sickle cell disease to try to decrease the number and severity of painful vaso-occlusive events and acute chest syndromes, and to reduce the need for blood transfusions.

While HU is well tolerated by most children and adults, it must be taken every day and requires additional clinic visits and blood count monitoring to ensure the patient’s safety.

HU is used primarily in children with sickle cell disease under five years of age who are already having frequent complications of their disease. Studies are underway to see if initiation of HU at an earlier age can help prevent these complications from occurring at all and to see if HU can replace the use of blood transfusions in patients with stroke or high TCD values.

With early identification by newborn screening, initiation of penicillin and routine immunizations, education of those involved in the child’s care, and lifelong, specialized follow up care, many of the complications of sickle cell disease can be prevented or managed promptly so that individuals can lead healthy, productive lives.

For more information about sickle cell disease in children and adults, visit http://www.SCInfo.org.

-- Sherri A. Zimmerman, MD, is an associate professor of pediatrics, a pediatric hematologist and member of the Governor's Council on Sickle Cell Syndrome.

-- Dennis Clements, MD, PhD, MPH, is the chief of primary care pediatrics at Duke Children's Hospital.