How Long is S-HPFH Testing After an FS Screen?

An ‘FS’ result on a newborn screen indicates that specialized genetic testing is needed to determine if your baby has a mild condition like Hereditary Persistence of Fetal Hemoglobin-Sickle Cell Disease (S-HPFH), or a severe form of sickle cell disease such as Sickle Cell Anemia (HbSS) or Sickle Beta-Zero Thalassemia ^[1]. This specialized genetic testing typically takes 2 to 4 weeks to process ^[2][3]. During this waiting period, medical guidelines recommend starting your baby on daily prophylactic penicillin by two months of age to protect them from severe infections, just in case they have a severe form of the disease ^[4].

Why the Wait Takes Several Weeks

When a newborn screen shows ‘FS’, it means the test detected Fetal hemoglobin (F) and Sickle hemoglobin (S) ^[5]. This specific pattern appears in severe sickle cell conditions, but it also perfectly matches the profile of the much milder S-HPFH ^[6]. Standard newborn screening tools cannot reliably tell these conditions apart at birth ^[1].

To get a definitive answer, your child’s doctor must order advanced genetic tests, such as DNA sequencing or MLPA (Multiplex Ligation-dependent Probe Amplification) ^[3]. These tests look deeply into your baby’s DNA for the specific genetic traits that cause HPFH, which protect the red blood cells from sickling ^[6]. Because these tests are highly specialized, the blood sample is usually shipped to a specific reference laboratory, meaning the results will take a few weeks to return ^[2].

The Crucial Role of Penicillin

The wait for these genetic results can cause immense anxiety for parents, but there is a clear, actionable step you can take to protect your newborn. Until an S-HPFH diagnosis is officially confirmed, medical guidelines mandate treating your baby as if they have severe sickle cell disease ^[4].

This means starting your newborn on prophylactic (preventative) penicillin typically by two months of age ^[7]. For infants with severe sickle cell disease, the spleen does not work properly, leaving them vulnerable to severe bacterial infections like Streptococcus pneumoniae ^[8]. Daily penicillin is a life-saving medication that drastically reduces this risk ^[8][7].

It is important to establish a solid routine so you do not miss a dose. Giving liquid medicine to a tiny baby can be stressful—they may spit up or drool. If your baby spits up a dose, or if you accidentally miss one, do not panic. Call your pediatrician or pharmacist for guidance on whether to re-administer the medication.

Fever is a Medical Emergency

While you wait for the genetic results, the most critical thing to watch for is a fever. A temperature of 100.4°F (38°C) or higher in a newborn with an ‘FS’ screen is a medical emergency ^[4]. Do not give fever-reducing medications; instead, seek immediate medical care (such as going to the nearest emergency room) so your baby can be evaluated and treated for any potential infections.

If the genetic test eventually confirms your baby has S-HPFH—a condition known for a very mild clinical course—your doctor will discuss whether it is safe to stop the penicillin ^[5][9]. Until that exact moment, the daily penicillin and prompt attention to fevers are your baby’s strongest shields.