Newborn Screening Test Positive? It May Be A False-Positive!

To best prepare ourselves for the arrival of our daughter, my wife and I took a few baby and parenting classes, we read books on the subject and researched the internet. The amount of information (and misinformation) available to new parents today is incredible, so we had to be selective and hence didn’t pay too much attention to stuff that could go wrong, including diseases and complications. With no family history of major disorders or genetic defects, we figured chances are, that everything is going to be just fine.

We were, however, aware of common procedures and issues with newborns such as:

Common Procedures

• Newborn hearing test (to make sure the baby’s hearing is OK, which is important for speech development)
• Newborn screening test (to catch genetic or metabolic diseases early)
• Vitamin K shot (to help with blood clotting until the baby’s Vitamin K production kicks in)
• Antibiotic eye ointment (to prevent infection caused by bacteria in the birth canal)
• Initial assessment of babies vital functions at 1 and 5 minutes after birth to determine the APGAR score (named after Dr. Virginia Apgar)

Common Issues

• Elevated bilirubin levels (Jaundice or yellow coloring of the skin caused by immature liver)
• Other minor skin defects (pimples, spots…)
• Hair-growth on body parts other than head (it’s called lanugo, is completely normal and disappears after a few weeks)
• Enlarged genitalia (due to mom’s hormones passed on to baby)

Every time I read something like “some babies may have XYZ condition (i.e., jaundice)” I naturally assumed that only applies to other babies, but not ours. So I set myself up for a surprise!

Newborn Screening Test

According to Baby’s First Test:

Newborn screening is a state public health service that reaches each of the more than 4 million babies born in the United States every year. It ensures that all babies are screened for certain serious conditions at birth, and for those babies with the conditions, it allows doctors to start treatment before some of the harmful effects happen.

Newborn screening is performed soon after the birth of your baby, and in most cases, while you are still in the hospital. All it takes is a few drops of blood and a simple hearing test.

In “Baby 411: Clear Answers & Smart Advice For Your Baby’s First Year” we read that the pediatrician is unlikely to discuss the test results unless at least one of the tests is positive. So we expected not to hear anything about newborn screening anymore after our baby’s blood was drawn at the hospital, one day after birth.

During the first week of our daughter’s life, we had appointments at our pediatrician, Dr. Michael Papciak and Dr. Rebecca Clements of Preston Ridge Pediatrics (who I can highly recommend), almost every day to check and make sure her weight went up and her bilirubin levels went down. Jaundice, caused by elevated Bilirubin levels causes newborns to be sleepier than usual, so they may not eat as much as they should and thus lose more weight than normal. Both checks went according to plan, but on day ten the pediatrician ordered an extra blood test and a second newborn screening test. He told us not to worry but explained that one of the newborn screening tests was positive. He elaborated that her 17-OHP levels were elevated, which triggered the test for Congenital Adrenal Hyperplasia (CAH) to be positive.

Congenital Adrenal Hyperplasia

I had never heard about such as disease and asked Dr. Papciak for a copy of the test report so I could do some research. We were still at the pediatrician when I googled for CAH. The first hit was a Wikipedia article that summarized CAH as:

Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands (steroidogenesis).
Most of these conditions involve excessive or deficient production of sex steroids and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults.

A genetic disorder involving sex steroids resulting in potentially altered sex characteristics (ambiguous genitalia ring a bell?)? I suddenly felt like hit by a train, and I wasn’t sure if and how I should tell my wife what I just learned.

Back at home I started doing some more research and learned that the most common form of CAH is caused by 21-hydroxylase (an enzyme) deficiency. Within this particular form there are three different types of CAH, which vary by severity level:

Salt-wasting CAH (classic form)

This is the most severe and common form (75% of patients affected by 21-hydroxylase deficiency have this form) and can lead to death within weeks, caused by the body excessively waste certain electrolytes. That’s why our pediatrician had our daughter’s Potassium, and Sodium levels tested right away. Since the levels were normal and she didn’t show any of the other symptoms (vomiting, lethargy…) we concluded that she was very likely not suffering from this form of CAH.

Simple Virilizing CAH  (classic form)

This form of CAH is less severe and typically manifests itself in ambiguous genitalia (girls may have an enlarged clitoris that looks like a penis), excessive hair growth, etc. Despite not being life-threatening it can lead to accelerated growth, but since the epiphyses fuse early, affected patients are often of a short stature; infertility and other issues.

We were told in the hospital as well as by our pediatrician that our daughter was physically OK (i.e., no penis and normal hair growth) but given the positive newborn screening test I couldn’t help but relate the hair on her back (lanugo) and her slightly enlarged genitalia (both normal for a newborn) to CAH. I even read a study about “Penile and Clitoral Sizes of Normal Full-Term Newborns in Korea” (I couldn’t find an equivalent study for newborns of Hispanic/Caucasian descent) to make sure our daughter’s genitalia was within normal range. It turned out to be within normal range, which meant she could only have a very mild form of Simple Virilizing CAH.

Late-onset CAH (non-classic form)

Late-onset CAH is the mildest form and as the name implies it sets on later in development and doesn’t necessarily and immediately affect newborns.

The more research I did, the more it became clear that reliable testing for CAH in newborns is not a simple task and the false-positive rate is quite high. Even Baby’s First Test points out that: “It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition.” Dr. Philip M. Farrell, a professor of pediatrics and population health sciences at the University of Wisconsin School of Medicine and Public Health estimated that 1 in 50 [newborn screening] tests are false-positives but for the disorder Congenital Adrenal Hyperplasia, there are between 100 and 200 false positives for every child truly affected.

That’s quite a high false-positive rate, and it gave us hope that our daughter’s test, too is a false-positive. To get more information about test procedures in Georgia I sent an email to Joanna Pringle, a Program Consultant at the Newborn Screening Unit of the Georgia Department of Public Health and she called me back within a few hours. She also forwarded my email to Angela Wittenauer, a Registered Nurse at the Genetics Lab of Emory University. She too called me back and confirmed that there are false-positives and that there is no need to be worried and we should wait for the results of the second test.

The negative result

About two weeks after the pediatrician sent in the blood sample for the second test we got the good news that the second test was negative and hence the first test was a false-positive caused by high cortisol levels in our daughter’s bloodstream a day after birth. The elevated cortisol levels were most likely caused by stress during delivery. Who knew that the delivery process was stressful for the baby :). Other reasons for a positive test result could be prematurity (preemies have naturally higher levels of 17-OHP) or simply a false-positive.

Bottom line: Every newborn is different, and a positive newborn screening or a failed hearing test may not mean anything. So stay calm, enjoy the nightly feedings and diaper changes and wait for the second test before freaking out!

Sources:

• CAH Diagnostic Dilemmas: Two Case Reports
• Baby’s First Test: Congenital Adrenal Hyperplasia
• Management Approaches to Congenital Adrenal Hyperplasia in Adolescents and Adults; Latest Therapeutic Developments
• Alternative Strategies for the Treatment of Classical Congenital Adrenal Hyperplasia: Pitfalls and Promises

Michael Kummer

Michael is a healthy living enthusiast and CrossFit athlete whose goal is to help people achieve optimal health by bridging the gap between ancestral living and the demands of modern society.