BQ Journal Vol 48 - Q3 2022 - 23

Early Release
Hospital admissions among children aged 0-4 and 5-11 years
during January 2019-March 2022 were identified using the
same ICD-10-CM codes as were used for ED data. Data on
pediatric liver transplants were obtained on May 20, 2022
from the national registry managed by OPTN; these included
monthly counts of liver transplants performed among patients
aged <18 years in the United States during January 2017-
March 2022, for whom the primary diagnosis at time of
transplant was acute hepatic necrosis of unknown etiology.**
Labcorp data, accessed on June 6, 2022, included deidentified
results for all stool specimens tested for adenovirus types
40/41†† (Logical Observation Identifiers Names and Codes
[LOINC] code 82209-8) among children aged 0-4 and
5-9 years during October 2017-March 2022.
Weekly numbers of ED visits during October 2021-
March 2022 were compared with a prepandemic baseline
(January 2018-February 2020) using a modified Farrington
Method§§ (5). Monthly hospitalizations and liver transplants
during October 2021-March 2022 were compared with those
for the same months (January-March and October-December)
during the calendar years 2017, 2018, and 2019, as available,
using the Wilcoxon rank sum test. Data on hospitalizations
and liver transplants during January 2020-September 2021
were excluded from each respective baseline because of possible
impacts of the COVID-19 pandemic. Monthly stool specimen
results are presented as total tests (all specimens with a negative
or positive result) and percentage positive for adenovirus types
40/41. The percentage of stool specimens testing positive for
adenovirus types 40/41 during October 2021-March 2022 was
compared with that during the same months (October-March)
of 2017-2018, 2018-2019, and 2019-2020, to minimize
potential effects of seasonality. Analyses were conducted in R
(version 4.1.1; R Foundation). This activity was reviewed by
CDC and was conducted consistent with applicable federal
law and CDC policy.¶¶
** Recipient diagnosis at the time of liver transplant was acute hepatic necrosis
(AHN) drug other specify; AHN etiology unknown; or AHN other, specify.
https://optn.transplant.hrsa.gov/patients/by-organ/liver/
†† Adenovirus types 40 and 41 are both associated with acute gastroenteritis.
Most commercial diagnostic tests do not distinguish between these two types.
§§ To monitor for recent anomalous increases in weekly trends, the modified
Farrington algorithm was applied to ED visits during the weeks ending January 6,
2018, through the week ending April 2, 2022, excluding a predefined early
pandemic period (weeks ending March 7, 2020, through October 2, 2021).
The modified Farrington algorithm has traditionally been used on weekly count
time series spanning multiple years. Weighted quasi-Poisson regression models
are fit to multiple year baselines with a time term and 10-level factor to account
for seasonality. The weighting strategy used by this algorithm is intended to
down-weight baseline observations associated with historical outbreaks. When
unweighted, baseline observations with abnormally high counts result in alerting
thresholds that are too high and a reduction in sensitivity.
¶¶ 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5
U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
Compared with a pre-COVID-19 pandemic baseline, no
increase in weekly ED visits with hepatitis-associated discharge
codes was observed during October 2021-March 2022
among children aged 0-4 or 5-11 years (Figure 1). During
January 2019-March 2022, a median of 22 (range = 9-29) and
10 (range = 4-19) hepatitis-associated hospitalizations among
children aged 0-4 and 5-11 years, respectively, were recorded
each month (Figure 2) (Supplementary Figure, https://stacks.
cdc.gov/view/cdc/118245). No significant changes were detected
in the number of hepatitis-associated hospitalizations during
October 2021-March 2022 compared with the same months
before the COVID-19 pandemic among children aged 0-4 years
(22 and 19.5, respectively, p = 0.26) or 5-11 years (12 and 10.5,
respectively, p = 0.42). A median of four (range = 0-10) liver
transplants occurred among persons aged <18 years each month
during January 2017-March 2022 (Figure 2) (Supplementary
Figure, https://stacks.cdc.gov/view/cdc/118245). No significant
increase in the number of monthly liver transplants was
observed during October 2021-March 2022 (five) compared
with the same months during 2017-2019 (four) (p = 0.19).
During October 2017-March 2022, the monthly number of
adenovirus tests ranged from 184 to 1,759 among children aged
0-4 years and from 140 to 725 among children aged 5-9 years
(Figure 3). Among both age groups, the number of adenovirus
tests was highest in March 2022. During October-March in
2017-2018, 2018-2019, and 2019-2020, the monthly percentage
of specimens positive for adenovirus types 40/41 ranged
from 5% to 19% among children aged 0-4 years and from
3% to 14% among children aged 5-9 years. After a decrease
in testing volume and percentage positive during April 2020-
September 2021, the percentage of specimens positive for adenovirus
types 40/41 during October 2021-March 2022 returned
to, but did not exceed, prepandemic levels in both age groups.
Discussion
Data from four large administrative databases were analyzed
to assess trends in pediatric hepatitis and percentage of stool
specimens positive for adenovirus type 40/41. These data
indicate that neither outcome has recently increased above pre-
COVID-19 pandemic levels. Although this ecologic analysis
cannot conclusively confirm or refute a potential association
between pediatric hepatitis and adenovirus, it provides useful
context for the ongoing investigation.
Data from two large electronic health record systems and
the liver transplant registry did not indicate an increase in
pediatric ED visits or hospitalizations associated with hepatitis
of unspecified etiology or pediatric liver transplants in the
United States. Historical data on pediatric hepatitis from other
countries are also limited. Although the United Kingdom has
observed increases in hepatitis among children aged 1-4 years
2
MMWR / June 14, 2022 / Vol. 71
Diagnostics I Pharmaceuticals I DxRx Solutions I Continuing Education I News
23
A Henry Schein Publication
https://stacks.cdc.gov/view/cdc/118245 https://stacks.cdc.gov/view/cdc/118245 https://stacks.cdc.gov/view/cdc/118245 https://optn.transplant.hrsa.gov/patients/by-organ/liver/
BQ Journal Vol 48 - Q3 2022

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