Multiple factors affect CK-MM blood test for DMD
Researchers study the creatine kinase-MM test used to screen newborns
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Various factors influenced the results of the creatine kinase-MM (CK-MM) blood test used to screen infants for Duchenne muscular dystrophy (DMD), according to a large study.
Factors that affected CK-MM levels included age at blood sample collection, gestational age, birth weight, sex, ethnicity, and seasonal temperature, data showed.
Newborn screening programs should be aware of these factors to reduce the occurrence of false-positive and false-negative results, the researchers recommended.
The large-scale study, “Factors Influencing Creatine Kinase-MM Concentrations in Newborns and Implications for Newborn Screening for Duchenne Muscular Dystrophy,” was published in the journal Clinical Biochemistry.
DMD is a genetic disorder marked by progressive muscle weakness and a loss of muscle mass. When DMD is suspected, blood tests can detect markers for muscle damage, such as creatine kinase (CK). Other methods, such as muscle biopsies and genetic tests, often are applied to confirm a DMD diagnosis.
Recently, the U.S. Food and Drug Administration (FDA) authorized a new screening test called GSP Neonatal Creatine Kinase-MM. It works by measuring the levels of a form of CK referred to as CK-MM, which is predominant in skeletal muscles that connect to bones to facilitate movement. That makes CK-MM more specific than total CK levels.
The test is fully automated and suitable for newborn screening (NBS) programs to support an early diagnosis. It can detect CK-MM levels in dried blood spots collected soon after birth and be used to detect other types of muscular dystrophy.
Still, large-scale data reflecting CK-MM levels in NBS programs is limited, and it is not clear whether factors such as birth weight and sex influence CK-MM levels.
“Any factors which cause variability in CK-MM levels must be considered when determining appropriate cut-off values for NBS,” wrote the team led by researchers based at the New York State Department of Health.
Analyzing pilot study data
To establish appropriate CK-MM screen cut-offs, or levels that support a DMD diagnosis, the team analyzed data from a pilot study launched to support NBS programs for DMD. During the two-year study, 36,781 newborns were screened for DMD using CK-MM. Data from 9,233 de-identified blood samples from newborns also were included and used to validate the CK-MM test in advance of the pilot study.
Blood tests revealed males had a higher mean level of CK-MM than female newborns — mean 495 vs. 467 nanograms per ml of blood (ng/mL). Adjusted statistical calculations found females had about 6% lower CK-MM levels than males.
Regarding gestational age (the time since the first day of the woman’s last menstrual cycle), CK-MM mean values were similar for extremely preterm infants (less than 28 weeks), very preterm (28-31 weeks, 6 days), and moderately preterm infants (32-33 weeks, 6 days).
By contrast, CK-MM mean values were significantly higher for late preterm babies (34 to 36 weeks, 6 days). Values were even higher for early term (37-38 weeks and 6 days) infants, those born at term (39-40 weeks, 6 days), late-term (41-41 weeks, 6 days), and post-term (42 weeks or more) babies. Each day longer in gestational age reflected about a 1.5% increase in CK-MM, with the highest levels seen in late-term babies.
Newborns with an extremely low birth weight (less than 1,000 g or 2.2 pounds) or very low birth weight (1,000-1,499 g or 2.2-3.3 pounds) had similar mean CK-MM values (109 and 95 ng/ml), while low birth weight infants (1,500-2,499 g or 3.3-5.5 pounds) had a higher mean CK-MM (280 ng/ml). Normal birth weight (2,500-3,999 g or 5.5-8.8 pounds) and high birth weight (4,000 g or 8.8 pounds or more) infants had significantly higher mean CK-MM levels than low birth weight newborns.
The highest CK-MM mean level was found at 24-25 hours of age for all weight categories, then dropped and stabilized after one week of life. Each hour increase in the age of the newborn at blood sample collection resulted in about a 3% decrease in CK-MM.
Ethnicities, temperatures also examined
Across different ethnicities, Black and Hispanic or Latino newborns had the lowest CK-MM values, while Asian newborns had the highest. Overall, Asians had about 18% higher CK-MM than non-Asians.
Finally, the researchers examined the impact of average daily temperature, collected from the U.S. National Weather Service, on CK-MM levels. There was a trend toward decreased mean CK-MM values with increasing temperature in New York City. During warmer months (June, July, August), the mean CK-MM values were 16.4% lower than in colder months (December, January, February).
“To reduce false positive and false negative cases, newborn screening programs should be cognizant of factors that influence CK-MM when determining cut-offs for the assay [test],” the team concluded. “Variability based on age at specimen collection and birth weight are primarily observed within the first week of life.”
“Therefore, particularly during this time period, multi-tiered cut-offs based on age of collection and lower cut-offs for premature and low birth weight babies are recommended,” they added. “Other cut-off determinants may include sex, race/ethnicity and seasonal temperature.”
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