What are we going to study?

1. Tokyo Twin Cohort Project(ToTCoP) :Its Beginning and Related Issues to be ConsideredJuko Ando, Ph.D. (Keio University), Chief researcherKoichi Nonaka ( Wako University), co-researcherNoriko Kato (National Institute of Public Health), co-researcherSyuichi Ooki ( Ishikawa Prefectural Nursing University), co-researcher

2. What are we going to study? Primary Aim: to clarify effects of genetic and shared/non-shared 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 …..

3. Saitama Narita Tokyo Tokyo Yokohama Chiba Kanagawa Coverage Area of ToTCoP • Tokyo Area = Tokyo Met. +Kanagawa +Chiba +Saitama (Pref.s)

4. 3339 2970 3031 2889 N of twin pairs born in Tokyo Area About 3000 pairs of twins are expected to be born per year within our research area

5. 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)

6. 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 We may have the necessary information … except for research fund Recently, the order of the list has been randomized in order to hide the family constitution. This has made our research impossible in the future!! We have to give up new recruitment from BRR.

7. 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

8. N of local governments • 13 well-trained assistants are transcribing the data in EACH municipal office.

9. 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

10. Schedule Building twin address list from BRR Pilot (9-14m) Main (3-14m) Sep↓ Registry/Cohort Entry 42m 48m 54m 9m 12m 15m 18m 24m 30m 36m 24m 12m 36m 48m Home interview Brain Imaging (OT) OT(NIRS), EEG DNA(all) 2004/11 2005/4 2006/4 2007/4 2008/4 2009/4 10 ToTCoP Cohort Full-scale Questionnaires Subcohorts

11. Pilot Main Subcohorts Announcement Request to Entry Full-scale Questionnaire (9-14 m.o.) Announcement Request to Entry Full-scale Questionnaires (9, 12, 15, 18, 24, 30, 36, … -14 m.o.) At Home At Laboratory … merged Address list transcribed from BRR

12. 2 moved Sending Entry Sheets 309 (April 1) Entry 178 (57.9%) Pilot study (from mid March,2005) Sending Fliers to 311 families with 9-14 month-old twins zygosity birth/current weight milk/food intake sleeping regularity etc… Sending Full-scale Questionnaire, IC Full-scale Questionnaire 122 (39.5%)

13. Response to Request to Entry (Pilot)

14. Response to Request to Entry 70 60 50 Accumulative Returned Entry Sheet (%) 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 20 40 60 80 100 120 140 Days from 1st RtoE 1sT Request to Entry 2nd R toE 3rd RtoE

15. Entry 658 (50.1 (55.6)%) Main study (from Sep,2005) Sending Fliers to 1001(Sep) & 310(Nov) families with 3-14 month-old twins Sending Entry Sheets 1313 zygosity 0,3,9 mo. weight, length, chest, head, milk intake sleeping regularity social behavior,etc… .. about to start this month Modified according to the results of Pilot study Full-scale Questionnaires for 9, 12, 15, 18, 24, 30, 36,.. month-old

18. 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.

19. Measures 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

20. Subcohorts # Observation and Interview at home # Optical Topography (OT) at laboratory

21. Triad of ToTCoP By the twins Central concern to the researchers Incentive to parents of the young twins Of the twins For the twins Much concern to parents and twins themselves

22. 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.

23. Twin A Twin A Twin B 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 H Z

24. Of the twins Much concern to parents and twins themselves 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?

25. 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.

26. 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

27. 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.

28. 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.

29. 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.