This Screening Life

Frederic W. Grannis Jr., MD

Earlier this year, baby A, at 2 months of age, underwent hematopoietic stem cell transplantation for severe immune compromise disease (SCID) at Memorial Hospital in New York City. As a thoracic surgeon who knew little about SCID, I had to read about this subject. I learned that the diagnosis of SCID is typically made during the first year of life following a number of severe infections. When I spoke with baby A’s relative Dr. Francis Cangemi, a medical school classmate and a prominent New Jersey retinal surgeon, he explained that in New York and a number of other states, all newborn children are routinely screened for SCID. Based on the screen, baby A received successful treatment, without complications related to pre-existing infections, and is recovering well. This case serves as an illustrative introduction to the impact of medical screening in our lives.

Bridget Kuehn has recently penned an informative historical review of neonatal screening in the pages of JAMA.[1] She described the initiation of neonatal screening for phenylketonuria by Dr. Robert Guthrie in the 1950s and went on to describe how based on recommendations from the March of Dimes and the Department of Health Services, all 4 million American neonates born yearly are screened for 28 separate diseases at an annual cost of only $30 per child. Kuehn informs us that 12,500 neonates are discovered to have metabolic abnormalities, and that early detection allows treatment to be initiated before complications and disability ensue.

SCID screening is recommended, but testing has not yet been implemented in most states.

In the state of California, the neonatal panel includes cystic fibrosis, biotinidase deficiency, galactosemia, primary congenital hypothyroidism, congenital adrenal hyperplasia, acylcarnitine panel, amino acid panel, hemoglobinopathies, and SCID. Kuehn suggests that alternative technologies offer promise for detection of many more rare metabolic abnormalities.

In fact, our screening lives begin before birth. (Although it was common in the past to require premarital blood screening for syphilis and other disease, this practice is rapidly disappearing.) Orange County, California pediatrician Dr. David Hicks, the neonatal intensive care unit director at St. Jude's Hospital in Fullerton, California, was kind enough to try to bring me up to date on current practice for prenatal and neonatal screening as follows.

Blood testing for maternal blood type, rubella, hepatitis B, VDRL, and vaginal group-B strep (at or beyond 36 weeks gestation) are routine in California. Other screening studies are based upon findings on maternal history and physical examination. Based upon a sexual history, HIV and herpes virus testing may be implemented. Family history is obtained with respect to muscular dystrophy, cystic fibrosis, thalassemia, neural tube defects, congenital heart disease, Huntington's chorea, Down syndrome, sickle-cell disease, autism, hemophilia, easy bleeding, and blood disorders. If any of these historical screens are positive, then the appropriate tests can be applied.

All mothers-to-be have a physical examination with emphasis on identification of factors that may increase fetal risk (eg, maternal age > 35, obesity, diabetes, advanced paternal age > 50).

Although no routine obstetrical ultrasound exam is mandated by the American College of Obstetrics and Gynecology, if high risk is identified, then ultrasound screening is highly recommended. A history of previous pregnancies with newborn illness and or fetal loss will increase the sensitivity for offering ultrasound, chorionic villus testing, or amniocentesis for genetic testing. (Many families choose not to do such testing if they would not terminate the pregnancy under any circumstances.)

Returning now to the delivery room, screening after birth is not just molecular. Dr. Hicks explains that following delivery, the first screen is a newborn exam by the nurse, often the first person to see the child, and then by the pediatrician/family doctor or neonatologist. The range of abnormalities that can be first identified with neonatal exam is wide and includes critical defects such as esophageal atresia and imperforate anus.[2] All newborns get a transcutaneous bilirubin check, moving on to a serum test if elevated past a certain level for age. All newborns will have a hearing test before discharge, the newborn blood screen will be done and, after the first 24 hours, a screen for complex/ductal-dependent congenital heart disease. A recent article published in Lancet discusses the value of screening oximetry in neonates for early detection of congenital heart disease.[3]

In the next few years of life, we undergo multiple well-baby medical exams. Periodic medical exams continue throughout childhood and adolescence. For example, my granddaughter was diagnosed with mild scoliosis during a screening examination at her school.

Health maintenance examinations include standard screening tests such as measurement of pulse rate (to screen for dysrhythmias), blood pressure (hypertension), intelligence quotient, tonsilar disease, heart murmurs, skeletal development, visual acuity, and many others.

Screening exams also take place at various landmarks in our lives: going away to camp, trying out for the football team, induction into military service, etc. We also are screened intermittently during travel and-if unwise and unlucky-by highway patrol officers for ethanol level.

During later adult life we are screened for hypertension, diabetes myocardial ischemia, and retinal disease. Finally, at the end of our days, we undergo a brief screen to confirm the absence of signs of life.

Although these tests can be a nuisance and can on occasion cause us distress, unnecessary follow-up testing or even complications, in general they help us to maintain health, function, and longevity. But there is significant push-back against this screening life.

In September 2013, I attended the “Preventing Overdiagnosis” International Conference at Dartmouth University and watched with dismay as a cadre of researchers and journal editors and their myrmidons relentlessly bashed screening as disruptive and harmful. In talk after talk they emphasized the negative aspects of screening. Attendees were cautioned that positive results cause anxiety and force primary physicians to spend precious time counseling the now “medicalized” patients. This process diverts time and dollars away from other aspects of public health. Worse, in the case of cancer, screening is purported to diagnose slow-growing, “resting” or “lanthanic” cancers that will not cause symptoms or kill during a normal anticipated life span. The audience was informed that overdiagnosis in turn leads to dangerous overtreatment. One speaker spoke against endoscopic screening for colon cancer, which he characterized as being “terrorized by the polyp police.”

Over breakfast a gray-haired, slender man visited our table and introduced himself in a Victor Borge accent. I told him that I was aware of who he was, Peter Goetzsche MD, co-founder of the Nordic Cochrane Centre. I asked him whether he had read the recent paper in Cancer that reported that more than 50% percent of breast cancer deaths in Massachusetts hospitals were in women under the age of 50 who had never had a mammogram.[4] I next asked him whether he felt any personal responsibility for these deaths, given that he had made frequent and strong recommendations against breast cancer screening in women between the ages of 40 and 49. He gave me an avuncular smile and assured me that although he had not read the article in question, it was “rubbish.” Later during his keynote address, he made clear that he does not recommend breast cancer screening to any woman, regardless of age.

It is difficult for me to reconcile such diametrically opposed views of the value of screening in our lives.

Dr. Cangemi wrote to New Jersey's governor, Chris Christie, about baby A and the importance of neonatal screening for SCID. He received a personal letter back from the governor, who agreed. True to his word, Gov. Christie recently signed legislation that mandates testing for SCID in New Jersey.

When baby A’s family gathered for dinner, they had justification for thanksgiving, with a good prospect that the child will survive his disease and go on to lead a long, happy, and productive life. One thing is undebatable, absent screening and effective treatment based on that screening, baby A would have had no such opportunity. Hopefully, doctors understand the benefits of screening and will not credit misinformation and overestimates of potential harms of medical screening, so that moving into the future, all infants, children, and adults in our society will continue to experience the benefits of screening.

References:

1. Kuehn BM. After 50 years, newborn screening continues to yield public health gains. JAMA. 2013;309:1215-1217.

2. Examination of the Newborn, a Practical Guide. Second Edition. Helen Baston and Hearher Durward. http://www.slideshare.net/AthilioReyes/examination-of-the-newborn-a-practical-guide-2010

3. Ewer AK, De-Wahl Granelli A, Manzoni P, et al. Pulse oximetry screening for congenital heart defects. Lancet. 2013;382:856-857.

4. Webb ML, Cady B, Michaelson JS, et al. A failure analysis of invasive breast cancer: Most deaths from disease occur in women not regularly screened. Cancer. 2013 Sep 9. [Epub ahead of print]