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The influence of seasonality and manufacturer kit lot changes on 17α-hydroxyprogesterone measurements and referral rates of congenital adrenal hyperplasia in newborns

Abstract

Newborn screening for congenital adrenal hyperplasia (CAH) is performed by measuring the concentration of 17α-hydroxyprogesterone (17-OHP) in dried blood spots. Unfortunately, the level of 17-OHP varies due to multiple factors, and therefore, the false positive rate for the test is a challenge. We analyzed screening data from 2007 to 2015 to determine the effect of seasonal changes and manufacturer kit lot changes on 17-OHP values and on numbers of infants referred. Data from screening 2.2 million infants over a 9-year period indicates that in the NYS during the colder months, daily mean 17-OHP values are higher, more retests are performed, and more infants are referred even though fewer infants are born. The practice of using fixed cutoffs for referring infants for CAH leads to more false positive results in colder months. In addition, there was an overall 10% increase in the daily mean 17-OHP values from the 2 years before and after a manufacturer kit lot change that occurred in November 2013, suggestive of a functional change in the kit at that time.

Conclusion: Newborn screening programs should be cognizant of seasonal temperature variations and (un)anticipated manufacturer kit changes because they may affect 17-OHP values and CAH referral rates.

What is Known:
• Newborn screening for congenital adrenal hyperplasia is generally performed by measuring 17α-hydroxyprogesterone (17-OHP) levels in dried blood spots.
• 17-OHP concentrations are affected by gestational age/weight of infant when specimen is collected, specimen collection time after birth, as well as race and sex of infant.
What is New:
• Seasonal temperature variations and unanticipated manufacturer kit changes affect 17-OHP levels and consequently referral rates in programs that use fixed cutoffs.
• Daily mean 17-OHP is generally higher when the ambient temperature is lower.

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Abbreviations

17-OHP:

17α-Hydroxyprogesterone

CAH:

Congenital adrenal hyperplasia

LBW:

Low birth weight

LOESS:

Local regression

NBS:

Newborn screening

NYC:

New York City

NYS:

New York State

PPV:

Positive predictive value

SV:

Simple virilizing

SW:

Salt wasting

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Acknowledgements

Newborn screening is funded by the State of New York. The authors wish to thank the Photography Unit at Wadsworth Center for assistance with the figures.

Authors’ contributions

MP was involved in acquisition of data and revising the manuscript. ED and AGD performed statistical analysis and were involved in revising the manuscript. MC was involved in interpreting data and revising the manuscript. NPT was involved in design of the work, analysis, and interpreting of data and drafting and finalizing the manuscript.

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Correspondence to Norma P. Tavakoli.

Ethics declarations

The manuscript is a retrospective case report that does not require ethics committee approval at our institution (Wadsworth Center, NYSDOH). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Communicated by Beat Steinmann

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Pearce, M., Dauerer, E., DiRienzo, A.G. et al. The influence of seasonality and manufacturer kit lot changes on 17α-hydroxyprogesterone measurements and referral rates of congenital adrenal hyperplasia in newborns. Eur J Pediatr 176, 121–129 (2017). https://doi.org/10.1007/s00431-016-2814-7

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  • DOI: https://doi.org/10.1007/s00431-016-2814-7

Keywords

  • Newborn screening
  • Congenital adrenal hyperplasia
  • 17α-Hydroxyprogesterone
  • Seasonal variation
  • Positive predictive value