Letters
considered an essential diagnostic adjunct in the workup of 4. Etchegaray A, Juarez-Peñalva S, Petracchi F, Igarzabal L. Prenatal genetic
all patients with sporadic perinatal CH.
William Sullivan, BS
Benjamin C. Reeves, BA
Phan Q. Duy, BS
Carol Nelson-Williams, MA
Weilai Dong, BS
Sheng Chih Jin, PhD
Kristopher T. Kahle, MD, PhD
Author Affiliations: Department of Neurosurgery, Yale School of Medicine,
New Haven, Connecticut (Sullivan, Reeves, Duy, Kahle); Department of
Genetics, Yale University School of Medicine, New Haven, Connecticut
(Nelson-Williams, Dong); Department of Genetics, Washington University
School of Medicine, St Louis, Missouri (Jin).
Corresponding Author: Kristopher T. Kahle, MD, PhD, Department of
Neurosurgery, Yale School of Medicine, 333 Cedar St, Tompkins 418,
New Haven, CT 06520 (kristopher.kahle@yale.edu).
Accepted for Publication: April 21, 2020.
Published Online: November 16, 2020. doi:10.1001/jamapediatrics.2020.4878
Author Contributions: Dr Kahle had full access to all of the data in the study
and takes responsibility for the integrity of the data and the accuracy of the data
analysis. Messrs Sullivan and Reeves were equal contributors.
Concept and design: Kahle, Jin.
Acquisition, analysis, or interpretation of data: Sullivan, Reeves, Duy,
Nelson-Williams, Dong, Jin.
Drafting of the manuscript: Kahle, Sullivan, Reeves.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Duy, Dong, Jin.
Obtained funding: Kahle, Jin.
Administrative, technical, or material support: Kahle, Nelson-Williams, Jin.
Supervision: Kahle, Jin.
Conflict of Interest Disclosures: None reported.
Funding/Support: Dr Kahle is supported by the Yale–National Institutes of
Health Center for Mendelian Genomics (5U54HG006504); R01 NS111029-01A1,
R01 NS109358, K12 228168, and the Rudi Schulte Research Institute. Dr Jin was
supported by the James Hudson Brown-Alexander Brown Coxe Postdoctoral
Fellowship, an American Heart Association Postdoctoral Fellowship, and the
National Heart, Lung, and Blood Institute of the National Institutes of Health
under award number K99HL143036 and R00HL143036-02. Messrs Reeves
and Duy are supported by the National Institutes of Health Medical Scientist
Training Program Training Grant T32GM136651.
Role of the Funder/Sponsor: The funding sources had no role in the design and
conduct of the study; collection, management, analysis, and interpretation of
the data; preparation, review, or approval of the manuscript; and decision to
submit the manuscript for publication.
Additional Contributions: We thank the patients and families who participated
in this research for their invaluable role in this study and the Hydrocephalus
Association (HA). We thank August Allocco, BS, Yale University, and Adam J.
Kundishora, MD, Yale School of Medicine, for their contribution to cohort
ascertainment, recruitment, and phenotypic characterization.
No compensation was received from a funding source for these
contributions.
Additional Information: The sequencing data for all congenital hydrocephalus
parent-offspring trios reported in this study have been deposited in the
National Center for Biotechnology Information database of Genotypes and
Phenotypes under the accession number phs000744.v4.p2.
1. Furey CG, Choi J, Jin SC, et al. De novo mutation in genes regulating neural
stem cell fate in human congenital hydrocephalus. Neuron. 2018;99(2):302-314.e4.
doi:10.1016/j.neuron.2018.06.019
2. Vos YJ, de Walle HEK, Bos KK, et al. Genotype-phenotype correlations in L1
syndrome: a guide for genetic counselling and mutation analysis. J Med Genet.
2010;47(3):169-175. doi:10.1136/jmg.2009.071688
3. Tully HM, Dobyns WB. Infantile hydrocephalus: a review of epidemiology,
classification and causes. Eur J Med Genet. 2014;57(8):359-368. doi:10.1016/
j.ejmg.2014.06.002
jamapediatrics.com
© 2020 American Medical Association. All rights reserved.
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considerations in congenital ventriculomegaly and hydrocephalus. Childs Nerv
Syst. 2020;36(8):1645-1660. doi:10.1007/s00381-020-04526-5
5. Xie B, Luo J, Lei Y, et al. Two novel pathogenic variants of L1CAM gene in two
fetuses with isolated X-linked hydrocephaly: A case report. Mol Med Rep. 2018;
18(6):5760-5764. doi:10.3892/mmr.2018.9583
6. Finckh U, Schröder J, Ressler B, Veske A, Gal A. Spectrum and detection rate
of L1CAM mutations in isolated and familial cases with clinically suspected
L1-disease. Am J Med Genet. 2000;92(1):40-46. doi:10.1002/(SICI)1096-8628
(20000501)92:1<40::AID-AJMG7>3.0.CO;2-R
Association of Home Quarantine and Mental Health
Among Teenagers in Wuhan, China, During
the COVID-19 Pandemic
Coronavirus disease 2019 (COVID-19) broke out in Wuhan,
China, in late 2019, and has become a pandemic.1 Unprec-
edented quarantine was imposed in Wuhan from January
23, 2020, to April 8, 2020, and all schools were closed.
Mental health associated with the quarantine is of great
concern, especially for adolescents. This study aimed to
investigate the prevalence of depression and anxiety and
their associations with lifestyle changes among adolescents
in Wuhan.
Methods | A cross-sectional study of a convenience sample
was conducted from March 30, 2020, to April 7, 2020, and
data were collected through an online questionnaire using
WeChat and QQ apps, which are widely used in China. Eligi-
bility criteria were (1) current residents in Wuhan, (2) age
between 12 and 18 years, and (3) not receiving a diagnosis of
severe acute respiratory syndrome coronavirus 2 infection.
There were 282 junior high schools (219 682 students) and
92 senior high schools (108 679 students) in Wuhan at the
time of the survey. We recruited 10 713 students (3.26%)
from 27 junior high schools (162 classes) and 11 senior high
schools (81 classes) (details of sampling and survey content
available on request). All participants provided written
informed consent for the survey. Ethics approval was
received from the Ethics Committee of the School of Public
Health at Fudan University.
The questionnaire collected information on sociodemo-
graphic factors and daily life factors during the lockdown pe-
riod. The Chinese-translated version of the Hospital Anxiety
and Depression Scale (HADS) was used to assess levels of anxi-
ety and depression symptoms.2,3 Descriptive and logistic re-
gression analyses were performed using SPSS statistical soft-
ware, version 20.0 (SPSS Inc). A 2-sided P value less than .05
was considered significant.
Results | Of 7890 participants, 4107 (52.1%) were female. The
prevalence was 21.7% (n = 1708) for anxiety and 24.6%
(n = 1941) for depression (HADS subscale score >7). Distribu-
tions of anxiety and depression according to sociodemo-
graphic factors are shown in Table 1.
Table 2 provides the results from logistic regression analy-
sis. After adjustment for covariates, going outside of the home,
food insufficiency, perceived discrimination, poor sleep qual-
ity, less face-to-face communication with family members, and
less pleasure or peace from interests/hobbies/specialties were
(Reprinted) JAMA Pediatrics March 2021 Volume 175, Number 3 313
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Table 1. Distributions of Anxiety and Depression According to Sociodemographic Factors

HADS, No. (%)a

Variable No. (%) Anxiety Depression
Total 7890 (100.0) 1708 (21.6) 1941 (24.6)
Sex
Male 3783 (47.9) 816 (21.5) 976 (25.8)
Female 4107 (52.1) 892 (21.7) 965 (23.5)
Age, y Abbreviation: HADS, Hospital Anxiety
12-14 2970 (37.6) 502 (16.9) 596 (20.1) and Depression Scale.
a
HADS is a 14-item scale that
15-16 2773 (35.1) 641 (23.1) 719 (25.9)
measures the presence of
17-18 2147 (27.2) 565 (26.3) 626 (29.2) symptoms related to anxiety (7
District of residence items) and depression (7 items)
during the past week. The
City 6190 (78.5) 1319 (21.3) 1498 (24.2)
maximum subscale score for both
Suburb 1700 (21.5) 389 (22.9) 443 (26.1) anxiety and depression is 21. The 2
Living with both parents or not subscales were both stratified as
follows: (1) scores from 0 to 7
Yes 1553 (19.7) 1357 (21.4) 1539 (24.3)
indicate normal case; (2) scores
No 6337 (80.3) 351 (22.6) 402 (25.9) from 8 to 10 indicate borderline
Father’s educational levelb case; and (3) scores from 11 to 21
indicate abnormal case. HADS
Low 5553 (70.4) 1260 (22.7) 1462 (26.3)
anxiety and HADS depression
High 2337 (29.6) 448 (19.2) 479 (20.5) represent borderline case and
Mother’s educational levelb abnormal case.4
b
Low 5857 (74.2) 1317 (22.5) 1509 (25.8) Low indicates educational level
below junior college; high indicates
High 2033 (25.8) 391 (19.2) 432 (21.2)
junior college or above.

significantly associated with increased risks of anxiety and de-
pression. More physical activity was significantly associated
with a lower risk of depression. The effect of home restric-
tions on study, screen time, and browsing information about
COVID-19 were significantly associated with an increased risk
of anxiety.
Discussion | During the COVID-19 quarantine period, more than
20% of adolescents had anxiety and depression. Long-term
home restrictions might have adverse effects on mental health
of adolescents because of a sharp change of lifestyles and vari-
ous stressors, such as fears of infection, frustration, and
boredom.5,6
This study revealed that anxiety and depression were
closely associated with daily life under home restrictions
among adolescents during the COVID-19 pandemic period, es-
pecially some factors that could be easily ignored, such as per-
ceived discrimination and ability to study. A multisectoral col-
laboration has been called on to pay attention to these
associations and to take necessary countermeasures.6
The study has several limitations. First, a convenient sam-
pling method could reduce a representativeness of the popu-
lation. Second, we were not able to evaluate some important
cofounding factors, such as levels of community support and
parents’ marital status. Third, a cross-sectional design pre-
vents us from assuming any causal relationships between home
quarantine–associated factors and the presence of anxiety or
depression.
The evidence may help guide the formulation of interven-
tion measures and effective and rapid response to an epi-
demic of novel infectious disease concerning the mental health
of adolescents.
Wei Li, PhD
Yuxin Zhang, MD
Jiwei Wang, PhD
Akihiko Ozaki, MD, PhD
Qingxiao Wang, MD
Yue Chen, PhD
Qingwu Jiang, MSc
Author Affiliations: School of Education, Huazhong University of Science &
Technology, Wuhan, China (Li, Q. Wang); School of Public Health, Key
Laboratory of Public Health Safety of the Ministry of Education and National
Health Commission Key Laboratory of Health Technology Assessment, Fudan
University, Shanghai, China (Zhang, J. Wang, Jiang); Medical Governance
Research Institute, Tokyo, Japan (Ozaki); School of Epidemiology and Public
Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
(Chen).
Corresponding Author: Jiwei Wang, PhD, School of Public Health, Fudan
University, No.130, Dong’an Road, Xuhui District, Shanghai, China 200030
(jiweiwang@fudan.edu.cn).
Accepted for Publication: July 29, 2020.
Published Online: January 19, 2021. doi:10.1001/jamapediatrics.2020.5499
Author Contributions: Drs Jiang and J. Wang had full access to all of the data in
the study and take responsibility for the integrity of the data and the accuracy
of the data analysis. Drs Li and Zhang contributed equally.
Concept and design: Li, J. Wang, Ozaki, Jiang.
Acquisition, analysis, or interpretation of data: Li, Zhang, J. Wang, Q. Wang,
Chen, Jiang.
Drafting of the manuscript: Li, Zhang, J. Wang, Jiang.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Li, Zhang, J. Wang.
Obtained funding: J. Wang.
Administrative, technical, or material support: Li, J. Wang, Jiang.
Supervision: J. Wang, Jiang.
Conflict of Interest Disclosures: Drs Ozaki receives personal fees from the
Medical Network Systems (MNES) outside the submitted work. No other
disclosures were reported.

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Table 2. Association Between Daily Life Characteristics and Anxiety and Depression

HADS, Adjusted odds ratio (95% CI)a

Variable Anxietyb Depressionb
Having ever gone out
No 1 [Reference] 1 [Reference]
Yes 1.19 (1.05-1.34)c 1.13 (1.00-1.27)d
Sufficiency of food
Sufficient 1 [Reference] 1 [Reference]
Somewhate 1.43 (1.26-1.63) 1.38 (1.22-1.57)
Insufficiente 1.86 (1.47-2.37) 1.70 (1.33-2.17)
Perceived discrimination
Never 1 [Reference] 1 [Reference]
Occasionallye 1.60 (1.39-1.85) 1.32 (1.15-1.52)
Oftene 2.11(1.82-2.44) 1.58 (1.37-1.82)
Sleep quality
Poor 1 [Reference] 1 [Reference]
Generale 0.44 (0.37-0.53) 0.49 (0.41-0.58)
Goode 0.22 (0.18-0.27) 0.23(0.20-0.28)
Abbreviation: HADS, Hospital Anxiety
Physical activity, d/wk and Depression Scale.
≤1 1 [Reference] 1 [Reference] a
Models are mutually adjusted for all
2-3 1.00 (0.87-1.16) 0.77 (0.67-0.89)e presented variables, including
demographic factors and all daily
≥4 1.01 (0.88-1.17) 0.73 (0.63-0.84)e
activity.
f
Effect on studying b
HADS is a 14-item scale that
Little 1 [Reference] 1 [Reference] measures the presence of
Somewhat 1.37 (1.17-1.60)e 1.11 (0.95-1.28) symptoms related to anxiety (7
e
items) and depression (7 items)
Great 2.82 (2.39-3.34) 1.91 (1.63-2.24)
during the past week. The
Score of screen time, points maximum subscale score for both
≤4 1 [Reference] 1 [Reference] anxiety and depression is 21. The 2
subscales were both stratified as
5-12d 1.27 (1.05-1.52) 1.16 (0.97-1.39)
follows: (1) scores from 0 to 7
13-24d 1.29 (1.05-1.60) 1.27 (1.04-1.56) indicate normal case; (2) scores
Browsing information about coronavirus disease from 8 to 10 indicate borderline
2019, h/d case; and (3) scores from 11 to 21
<0.5 1 [Reference] 1 [Reference] indicate abnormal case. HADS
anxiety and HADS depression
0.5-2 1.24 (1.09-1.40)c 1.04 (0.92-1.18)
represent borderline case and
>2 1.82 (1.38-2.40)e 1.67 (1.26-2.21)d abnormal case.4
c
Face-to-face communication, h/d Statistically significant (P < .01).
d
<0.5 1 [Reference] 1 [Reference] Statistically significant (P < .05).
e
0.5-2 0.83 (0.73-0.95)c 0.64 (0.56-0.73)e Statistically significant (P < .001).
f
>2 0.77 (0.64-0.93)c 0.53 (0.44-0.63)e Effect on studying means the
influence of home restrictions on
Seeking pleasure from interests
studying, such as being unable to
Occasionally 1 [Reference] 1 [Reference] communicate effectively with
Sometimese 0.72 (0.61-0.85) 0.52 (0.45-0.61) teachers and classmates and unable
to concentrate and inefficient in
Oftene 0.65 (0.55-0.76) 0.25 (0.22-0.30)
learning.

Funding/Support: This study was supported by the Shanghai Health and
Planning Commission’s fourth round of public health 3-year action plan (project
15GWZK1001) and the Independent Innovation Research Foundation of
Huazhong University of Science and Technology (Humanities and Social
Sciences) (project 2017WKYXQY009).
Role of the Funder/Sponsor: The funders had no role in the design and
conduct of the study; collection, management, analysis, and interpretation of
the data; preparation, review, or approval of the manuscript; and decision to
submit the manuscript for publication.
Additional Contributions: We thank Jinming Yu, PhD (School of Public
Health, Fudan University, Shanghai, China), for assistance in the original
study design. We would like to acknowledge assistance from Tetsuya Tanimoto,
MD (Medical Governance Research Institute, Tokyo, Japan), Yasuhiro Kotera,
MA (University of Derby, Kedleston Road, Derby, United Kingdom), and
Toyoaki Sawano, MD (Sendai City Medical Center, Sendai, Miyagi, 983-0824,
Japan), in writing and revising the manuscript. These individuals were not
compensated.
1. Xiang YT, Jin Y, Cheung T. Joint international collaboration to combat mental
health challenges during the coronavirus disease 2019 pandemic. JAMA Psychiatry.
2020;77(10):989-990. doi:10.1001/jamapsychiatry.2020.1057
2. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta
Psychiatr Scand. 1983;67(6):361-370. doi:10.1111/j.1600-0447.1983.
tb09716.x
3. Chan YF, Leung DY, Fong DY, Leung CM, Lee AM. Psychometric evaluation of
the Hospital Anxiety and Depression Scale in a large community sample of
adolescents in Hong Kong. Qual Life Res. 2010;19(6):865-873. doi:10.1007/
s11136-010-9645-1

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4. Ciprandi G, Schiavetti I, Rindone E, Ricciardolo FL. The impact of anxiety and
depression on outpatients with asthma. Ann Allergy Asthma Immunol. 2015;115
(5):408-414. doi:10.1016/j.anai.2015.08.007
5. Brooks SK, Webster RK, Smith LE, et al. The psychological impact of
quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020;
395(10227):912-920. doi:10.1016/S0140-6736(20)30460-8
6. Wang G, Zhang Y, Zhao J, Zhang J, Jiang F. Mitigate the effects of home
confinement on children during the COVID-19 outbreak. Lancet. 2020;395
(10228):945-947. doi:10.1016/S0140-6736(20)30547-X
Screening and Severity of Coronavirus Disease 2019
(COVID-19) in Children in Madrid, Spain
As the pandemic of coronavirus disease 2019 (COVID-19)
spreads, new data emerge and understanding of the disease
improves. Reports associated with children are growing but still
scarce.1-3 The epicenter of the epidemic has displaced to
Europe. The first case in Spain was declared on January 31,
2020, and the first case in the Madrid region was declared on
February 27, 2020.
Methods | With the aim of obtaining an overview of the pro-
portion of confirmed cases among those tested and the
severity of the disease in children, a registry of tested cases
was performed from March 2, 2020, to March 16, 2020, by
pediatricians in 30 secondary and tertiary hospitals in
Madrid, Spain, during the first 2 weeks of the epidemic.
Children were screened according to Spanish Public Health
recommendations, which included those patients with a
significant disease who were admitted, or likely to be admit-
ted, at the time of evaluation according to the attending
pediatrician or patients with signs or symptoms compatible
with COVID-19 and the risk of complications due to baseline
disease. This study was approved by the ethics committee
of Hospital 12 de Octubre. Data collection was allowed by
verbal consent with subsequent written consent provided
by patients with positive results. Data were deidentified.
The test used for diagnosis was real-time polymerase chain
reaction. 4 The reported sensitivities for the E gene and
RdRp gene assays are 5.2 and 3.8 copies per reaction at 95%
detection probability, respectively.4 Both genes needed to
be amplified to report a positive result.
Results | During the first 2 weeks of the epidemic in Madrid,
Spain, 365 children were screened within the 30 hospitals. Dur-
ing the first week, 6 of 103 patients (5.8%) had positive test re-
sults. At the end of the second week, 41 of 365 patients (11.2%)
had positive test results (Table). By March 16, 2020, 41 of the
4695 confirmed cases (0.8%) in Madrid region were children
younger than 18 years.
The median age of the tested patients was 3 years (inter-
quartile range, 0.9-6 years; range, 0-15 years) and the
median age of the patients with positive results was 1 year
(interquartile range, 0.35-8.5 years; range 0-15 years).
Twenty five of 41 children with confirmed COVID-19 (60%)
were hospitalized, 4 of 41 (9.7%) were admitted to a pediat-
ric intensive care unit (PICU), and 4 of 41 (9.7%) needed
respiratory support beyond nasal prongs (Table). Of these,
1 of 4 (25%) had only 1 previous condition (recurrent wheez-
ing). No patients died. Initial syndromic diagnoses were

Table. Clinical Features of Participants Tested for Severe Acute Respiratory Syndrome Coronavirus 2

No. (%)
Positive Negative
Features (n = 41) (n = 324) P valuea
Sex
Female 23 (56) 134 (41.3)
Male 18 (44) 143 (44.1) .35
NA 0 47 (14.5)
Contact with person with confirmed case
Yes 16 (39) 49 (15.1)
<.001
No/community transmission 25 (61) 275 (84.8)
Hospitalization
Yes 25 (60) 218 (68)
.41
No 16 (40) 106 (32)
PICU admission
Yes 4 (10) 18 (5.5)
.28
No 37 (90) 306 (94.4)
Respiratory support beyond oxygen in nasal prongs
Yes 4 (10) 7 (2.1)
No 37 (90) 317 (97.8)
High-flow ventilation 1 (2) 6 (1.8) <.001
Noninvasive ventilation 2 (5) 0
Mechanical ventilation 1 (2) 1 (0.3)
Underlying disease Abbreviations: NA, data not available;
PICU, pediatric intensive care unit.
Yes 11 (27) 50 (15.4)
.06 a
The P value was calculated as χ2
No 30 (73) 274 (84.5)
with Fisher correction as needed.

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