ORIGINAL
ARTICLES
Clinical Impact and Cost Ef?cacy of Newborn Screening for Congenital
Adrenal Hyperplasia
Danya A. Fox, MD, FRCPC, MPH1,*, Rebecca Ronsley, MD, FRCPC1,*, Asif R. Khowaja, PhD2, Alon Haim, MD3,
Hilary Vallance, MD, FRCPC, FCCMG4, Graham Sinclair, PhD, FCCMG4, and Shazhan Amed, MD, FRCPC, MScPH1
Objectives To evaluate the clinical impact of a congenital adrenal hyperplasia (CAH) newborn screening program
and incremental costs relative to benefits in screened vs unscreened infants. We hypothesized that screening would
lead to clinical benefits and would be cost effective.
Study design This was an ambispective cohort study at British Columbia ChildrenàHospital, including infants
diagnosed with CAH from 1988-2008 and 2010-2018. Data were collected retrospectively (unscreened cohort)
and prospectively (screened cohort). Outcome measures included hospitalization, medical transport, and resuscitation requirements. The economic analysis was performed using a public payer perspective.
Results Forty unscreened and 17 screened infants were diagnosed with CAH (47% vs 53% male). Median days to
positive screen was 6 and age at diagnosis was 5 days (range, 0-30 days) and 6 days (range, 0-13 days) in unscreened and screened populations, respectively. In unscreened newborns, 55% required transport to a tertiary
care hospital, 85% required hospitalization, and 35% required a fluid bolus compared with 29%, 29%, and 12%
in screened infants, respectively. The cost of care was $33 770 per case in unscreened vs $17 726 in screened newborns. In the screened cohort, the incremental cost-effectiveness ratio was $290 in the best case analysis and
$4786 in the base case analysis, per hospital day avoided.
Conclusions Compared with unscreened newborns, those screened for CAH were less likely to require medical
transport and had shorter hospital stays. Screening led to a decrease in hospitalization costs. Although screening
did not result in cost savings, it was assessed to be cost effective considering the clinical benefits and incremental
cost-effectiveness ratio. (J Pediatr 2020;220:101-8).
C
ongenital adrenal hyperplasia (CAH) is a group of autosomal-recessive conditions caused by an enzymatic defect in the
adrenal gland leading to impaired cortisol synthesis. In Canada and the US, the incidence is estimated to be 1:15 000.1
More than 90% of cases result from a deficiency of 21-hydroxylase, an enzyme required for the synthesis of cortisol and
aldosterone leading to an accumulation of steroid precursors, including 17a-hydroxyprogesterone (17OHP). CAH is subdivided into the salt wasting variant, defined by insufficient aldosterone production, and the simple virilizing variant, characterized by adequate aldosterone production, with a frequency of 75% and 25%, respectively.2 CAH may present in a salt wasting
crisis, marked by dehydration, hyponatremia, hyperkalemia, and potentially shock. These crises generally occur in the first
month of life and may be fatal if not treated promptly.3,4
In the US, newborn screening (NBS) for CAH is currently performed in all states.5 In Canada, 5 provinces and at least some
regions of all 3 territories include CAH in their NBS programs. Several large studies have corroborated that screening leads to
earlier diagnosis of CAH, particularly for males who lack the genital ambiguity that is typically easily identifiable in females.6-9
Despite this evidence, certain regions have left CAH out of their NBS programs, most notably the United Kingdom.10 Reasons
include the high rate of false positives in premature newborns and the limited benefits of testing for females.11,12 Determining
whether screening for CAH is cost effective may help NBS programs to make
informed decisions as to whether the disease should be added to their panel.
However, there are few published data on the cost efficacy of this screen.13-15
From the Department of Pediatrics, and School of
The recent clinical practice guidelines for CAH highlight the paucity of knowlPopulation and Public Health, University of British
edge in this field.16 The 2 studies cited had strikingly different results of
Columbia; Pediatric Endocrinology Unit, Department of
1
2
3
Pediatrics, Soroka Medical Center, Ben-Gurion
University of the Negev, Beer-Sheva, Israel; and 4BC
Newborn Screening Program, Department of Pathology
and Laboratory Medicine, British Columbia ChildrenÊHospital, Vancouver, British Columbia, Canada
BC
CAH
ICER
ICU
NBS
17OHP
British Columbia
Congenital adrenal hyperplasia
Incremental cost-effectiveness ratio
Intensive care unit
Newborn screening
17a-hydroxyprogesterone
*Contributed equally.
Funded by a Department of Pediatrics Resident
Research Grant, University of British Columbia, 2011.
The funders had no role in any aspect of the study nor the
preparation of the manuscript. The authors declare no
conflict of interest.
0022-3476/$ – see front matter. 2019 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.jpeds.2019.12.057
101
THE JOURNAL OF PEDIATRICS www.jpeds.com
$20 000 and $255 700 – $292 000 per quality-adjusted lifeyear, leaving it unclear as to whether screening for CAH is
cost effective.13,15
In British Columbia (BC), CAH was added to the NBS
program in 2010. Through this study, we sought to evaluate
the clinical impact of screening for CAH and the cost effectiveness by comparing cohorts of screened and unscreened
newborns. We hypothesized that screening would result in
clinical benefits and would be cost effective.
Methods
BC ChildrenàHospital is the only tertiary care hospital in the
province of BC and is located in Vancouver, Canada. The division of endocrinology at the hospital is contacted by the
NBS laboratory for every positive CAH screen. The endocrinologists at BC ChildrenàHospital provide care to the majority of patients with CAH, although a small number of
patients are managed by community endocrinologists.
NBS Program
This program covers BC, as well as the Yukon Territory (
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