Transcript 東京双生児コホートプロジェクト Tokyo Twin Cohort Project

Tokyo Twin Cohort Project (ToTCoP) :
Its Beginning and Related Issues to be Considered
Juko Ando, Ph.D. (Keio University), Chief researcher
Koichi Nonaka ( Wako University), co-researcher
Noriko Kato (National Institute of Public Health), co-researcher
Syuichi Ooki ( Ishikawa Prefectural Nursing University), co-researcher
What are we going to study?
Primary Aim: to clarify effects of genetic and shared/nonshared environmental factors on the early-stage of human
development in terms of temperament, motor skills,
cognitive-linguistic abilities, and other behavioral traits.
ToTCoP cohort:
Longitudinal follow-up by questionnaires to new born twin
population in Tokyo metropolitan area
Subcohorts (subsets of ToTCoP cohort):
# Observation and Interview at home
# Optical Topography (OT) at laboratory
…..
Coverage Area of ToTCoP
• Tokyo Area
= Tokyo Met.
+Kanagawa
+Chiba
+Saitama (Pref.s)
Saitama
Tokyo
Tokyo
Narita
Yokohama
Chiba
Kanagawa
N of twin pairs born in Tokyo Area
1400
1200
297
0
1000
333
9
288
9
303
1
Tokyo
Kanagawa
Chiba
Saitam
800
600
400
200
0
1999
2000
2001
2002
About 3000 pairs of twins are expected to be born
per year within our research area
Ideal
Population-based Twin Cohort
5-year Follow-up from Infancy
Realistic?
In Japan, there is no population (electronic) registry available to researchers.
The Basic Resident Registration (BRR) (Open to Public Reading)
BRR: Is it useful to twin study?
BRR: reflecting the whole population in each area
Possible source for complete recruiting (no sampling, no selection biases)
BRR: printed on a family-basis with the information on name, sex, birthdate
Possible source for identifying twins by the members with the same birthdates
Recently, the order of the list has been randomized
We may have the necessary information
in order to hide the family constitution. This has
made our …
research
impossible
in the future!! We
except for
research fund
have to give up new recruitment from BRR.
BRR: Its practical limitation as a
source of the population list
BRR: Transcription by hand is necessary for each district
We cannot obtain the list for the whole area at once, giving different
time-frame of recruiting for different district
BRR: New born babies are not registered instantly,
usually with a time-lag of 3 months or more
Youngest subjects are usually at age 6 months or more,
thus on-going information on the first half year of life is hardly obtained
Actually quasi-population-based newborn recruiting
with a different time frame for each district
N of local governments
ward city village town total
•
Tokyo
23
26
1
3
53
Kanagawa
25
17
1
17
60
Chiba
6
32
5
39
82
Saitama
10
39
4
41
94
Total
64
114
11
100
289
13 well-trained assistants are transcribing the data in EACH municipal office.
Information transcribed from BBR
•
•
•
•
name
residential address
date of birth
sex
• Expected twins, triplets, quadruplet, quintuplet
= individuals with same address and same date of
birth
Schedule
2004/11
2005/4
2006/4
2007/4
ToTCoP Cohort
2008/4
2009/4
Building twin address
list from BRR
Pilot
(9-14m)
Sep↓
Registry/Cohort
Main
(3-14m)
Entry
9m
12m
15m
18m
24m
30m
36m
42m
48m 54m
Full-scale Questionnaires
Subcohorts
Home interview
Brain Imaging
(OT)
12m
24m
36m
OT(NIRS), EEG
48m
DNA(all)
10
Address list transcribed from BRR
Pilot
Main
Announcement
Announcement
Request to Entry
Request to Entry
Full-scale
Questionnaire
Full-scale
Questionnaires
(9-14 m.o.)
(9, 12, 15, 18, 24, 30,
36, … -14 m.o.)
merged
Subcohorts
At Home
At Laboratory
…
Pilot study (from mid March,2005)
Sending Fliers
to 311 families with
9-14 month-old twins
2 moved
Sending Entry Sheets
309 (April 1)
zygosity
birth/current weight
milk/food intake
sleeping regularity
etc…
Entry
178 (57.9%)
Sending Full-scale Questionnaire, IC
Full-scale Questionnaire
122 (39.5%)
Response to Request to Entry (Pilot)
Response to Request to Entry
Accumulative Returned Entry Sheet (%)
70
60
50
40
30
Pilot Entry Apr 2005
Announcement & RtoE
Main Entry(1) Sep 2005
20
Main Entry(2) Nov 2005
Pilot late-comers Nov 2005
10
Announcement
0
-20
0
1sT Request to Entry
20
2nd R toE
40
60
3rd RtoE
80
100
120
Days from 1st RtoE
140
Main study (from Sep,2005)
Sending Fliers
to 1001(Sep) & 310(Nov) families with
3-14 month-old twins
zygosity
0,3,9 mo.
weight, length, chest, head,
milk intake
sleeping regularity
social behavior,etc…
Modified according
to the results of
Pilot study
Sending Entry Sheets
1313
Entry
658 (50.1 (55.6)%)
Full-scale Questionnaires
for 9, 12, 15, 18, 24, 30, 36,.. month-old
.. about to start
this month
Response to Full-scale Study (Pilot)
Cumulative Proportion of Returned
Questionnaire (%)
90.0
almost 80% to the population
giving consent to Entry
80.0
70.0
60.0
c.a. 45% to the registered mother population
50.0
40.0
to Entry population
30.0
Dates of sending questionnares
according to birthdate of the twins
20.0
To Registered population
10.0
Date for sending request
0.0
0
50
100
150
Days
200
250
300
Present Statistics of ToTCoP cohort
as of 13 Jan 2006
Request dates
Total (pairs)
Birth Age in
% to
date month DB Req Entry %
DB
Oct-05
3
1
1
1
100.0
Sep-05
4
2
0
0
0.0
Aug-05
5
19
6
3 50.0 15.8
Jul-05
6
27
8
4 50.0 14.8
Jun-05
7
46
21
10 47.6 21.7
May-05
8
69
40
17 42.5 24.6
Main3 Apr-05
9
67
50
29 58.0 43.3
(2006 Mar-05 10
96
79
54 68.4 56.3
Main2 Jan)
Feb-05 11
109
85
49 57.6 45.0
(2005
Jan-05 12
125 101
53 52.5 42.4
Main1 Nov)
Dec-04 13
175 145
84 57.9 48.0
(2005
Nov-04 14
178 160
69 43.1 38.8
Sep)
Oct-04 15
183 172 100 58.1 54.6
Sep-04 16
176 160
82 51.3 46.6
Aug-04 17
185 147
83 56.5 44.9
Jul-04 18
218 152
87 57.2 39.9
Jun-04 19
229 207
84 40.6 36.7
Pilot
May-04 20
182 169
75 44.4 41.2
Pilot
(late
Apr-04 21
205 178
82 46.1 40.0
(2005
comer)
Mar-04 22
205 184
75 40.8 36.6
Mar)
(2005
Feb-04 23
218 194
84 43.3 38.5
Nov)
Jan-04 24
202 185
70 37.8 34.7
Total 2917 2444 1195 48.9 41.0
What are the Research Questions?
# Full-scale questionnaires are now being made
and brushed up.
# Procedures for subcohort studies are now
preliminarily on-going.
# The followings are the present research frame.
Measures
month
9 mo
12 mo
15 mo
18 mo
24 mo
30 mo
36 mo
42 mo
48 mo
54 mo
Physiques
Stressful Life Events
○
○
○
○
○
○
○
○
○
○
○
DenverII
○
○
○
Zygosity
Laterality
Motor Development
Temperament
Autisitic Symptoms
Social Behavior
Sleeping Behavior
Conduct Disorder
Nutrition
Cognition
Triad Interaction
Language
Attachment
Cultural/Educational
Environment
Parental Behavior
Home Environment
Twin Situation
Depressive Symptom
Parental Stress
Marital Love
Social Support
○
○
○
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DenverII
IBQ-R
M-CHAT
○
MAI
ECBQ
PTCI
CBQ
Yale
Yale
M-CHAT
M-CHAT
Screener
Screener
BISQ
BISQ
CBCL
CBCL
○
○
Bayley
Bayley
Bayley
○
○
○
○
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MAI
○
○
EES
○
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CBCL
WISC-R
○
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○
○
○
○
○
EES
○
SDS
PSI
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SDS
○
SDS
○
SDS
SDS
PSI
○
○
PTCI
○
○
○
○
○
○
DENVER Ⅱ=behavioral development,IBQ-R/ECBQR/CBQ=Rothbart’s temperament Scales PTCI=Preschool Temperament & Character Inventory、
BISQ=Brief Infant Sleep Questionnaire CBCL=Child Behavior Check List、MAI=Maternal Attachment Instrument,
EES=Evaluation of Environment Stimulus SDS=Self-Rating Depression Scale PSI=Parental Stress Inventory
Subcohorts
# Observation and Interview at home
# Optical Topography (OT) at laboratory
Triad of ToTCoP
Central
concern to the
researchers
By
the twins
Incentive to
parents of the
young twins
Of
the twins
For
Much concern to
parents and twins
themselves
the twins
By
the twins
Central
concern to the
researchers
TWIN STUDY METHOD by comparing MZ
and DZ twins, NOT singletons
# Only twins are necessary.
# Appropriate proportion of MZ and DZ for the method?
Representativeness of underlying population is
NOT necessary.
# Burden of too many items in the questionnaires may inhibit continuous entry.
# “HZ issue” was checked at the pilot study.
H
Z
Twin A
Twin B
Twin A
Twin B
Question 1
Question 1
Question 1
Question 1
Question 2
Question 2
Question 2
Question 2
Question 3
Question 3
Question 3
Question 3
Question 4
Question 4
Question 4
Question 4
LOW contrast between co-twins
HIGH contrast between co-twins
Of
Much concern to
parents and twins
themselves
the twins
Parents are interested in Being TWINS,
compared with being a SINGLETON
# ToTCoP does not have original comparative singleton families.
# Representativeness of underlying population is NECESSARY for adequate
estimation of the status-quo of the whole twin families.
# Response proportion is critical. 40-60% is enough?
For
the twins
Incentive to parents
of the young twins
Parents are quite busy in rearing twin babies for
the first few years, with the nuclear families
tending to be isolated from appropriate
information or official help
# ToTCoP does not have enough resources to help directly each family.
# But, we have to give information as much as possible to facilitate healthy
growing of the twins.
# This is not for science, but for the welfare of the families. What if we give
information to change parental behaviors?
# It is ethically necessary, if we should lose scientific objectivity.
Feedback to Participants
•
•
•
•
•
Periodical Newsletters (3 issues per year)
Hint cards on rearing twin children (mail)
Web page information (only in Japanese)
Introduction to circles for twin’s parents
Individual feedback assessment on
physics (specific to twins) and other
psychological and environmental indices.
• Information exchange meeting for the
participants
Informed Consent and Ethical Issues
• Written IC is obtained at the 1st full-scale
questionnaire.
• Participants to other subcohort programs
are requested to give IC for each program.
• ToTCoP program and other subcohort
programs are to be assessed beforehands
at the institutional ethical committee.
Data management
• Participant’s basic information transcribed
from BRR is maintained with ID number by
FileMaker Pro installed on an off-line PC.
• Data from questionnaires are entered as a
text file with ID number, and shared within
the ToTCoP researchers by Web disk.
• Data handling specific to twin data is the
critical issue to be considered A.S.A.P.
Finally …
# Asian population has, in general, an advantage of
a higher relative proportion of MZ twins for more
accurate estimation of genetic/environmental
contribution.
# ToTCoP should make every effort to keep higher
participating proportion in order to take the
advantage of its population-based origin, as well as
to obtain longitudinal follow-up data as much as
possible for its research questions on human early
development.