Cohort Profile
Cohort Profile: The Western Australian
Pregnancy Cohort (Raine) Study–Generation 2
Leon Straker,
1
* Jenny Mountain,
2
Angela Jacques,
2
Scott White,
3
Anne Smith,
1
Louis Landau,
4
Fiona Stanley,
5
John Newnham,
6
Craig Pennell
6
and Peter Eastwood
7
1
School of Physiotherapy and Exercise Science, Curtin University, Perth, WA, Australia,
2
School of
Population Health, University of Western Australia, Perth, WA, Australia,
3
Maternal Fetal Medicine
Service, King Edward Memorial Hospital, Perth, WA, Australia,
4
School of Medicine and
Pharmacology, University of Western Australia, and Department of Health, Government of Western
Australia, Perth, WA, Australia,
5
Telethon Kids Institute, Perth, WA, Australia,
6
School of Women’s and
Infant’s Health and
7
Centre for Sleep Science, School of Anatomy, Physiology and Human Biology,
University of Western Australia, Perth, WA, Australia.
*Corresponding author. School of Physiotherapy and Exercise Science, Curtin University, GPO Box U1986, Perth, WA,
Australia. E-mail: L.Straker@curtin.edu.au
Accepted 13 September 2016
Why was the cohort set up?
The Western Australian Pregnancy Cohort (Raine) Study
(www.rainestudy.org.au) was established 1989-1991 with
the then stated purpose:
to develop a large cohort of Western Australian children
studied from 18 weeks’ gestation to ascertain the relative
contributions of familial risk factors, fetal growth, placen-
tal development and environmental insults to outcome in
infancy and to the precursors of adult morbidity. This co-
hort, with complete intrauterine, perinatal and childhood
data, will enable evaluation of the interaction between
these factors, subsequent lifestyle patterns and environ-
mental exposures which contribute to ill health during
life.
1
Establishment of the cohort involved combining fund-
ing for ‘a randomised controlled trial of the influence of
serial fetal ultrasounds on birth outcomes’ from the
National Health and Medical Research Council of
Australia
2
and funding to investigate ‘the origins of disease
in the fetus, the child and the young adult’ from the Raine
Medical Research Foundation.
1
The conceptual framework for the study was initially
based around the developmental origins of health and dis-
ease, but has since evolved into a life-course framework
taking into account the multiple interacting domains of
genetics, phenotypes (cardiometabolic, respiratory, im-
munological, hormonal, musculoskeletal, psychological,
vision and hearing, body composition and growth), behav-
iours (physical activity, sedentary behaviour, sleep, diet,
drug use, risk taking), the environment (sunlight, chemical
exposures, spatial environment) and other developmental
outcomes (education, work).
Who is in the cohort?
Pregnant women presenting at the public antenatal clinic
at King Edward Memorial Hospital (at that time it was the
only tertiary women’s and infants’ hospital in Perth,
Western Australia) and nearby private practice clinics be-
tween May 1989 and November 1991
3
were invited to
participate. Women were invited if they were between 16
and 20 weeks pregnant, had sufficient proficiency in
V
C
The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Assoc iation 1384
International Journal of Epidemiology, 2017, 1384–1385j
doi: 10.1093/ije/dyw308
Advance Access Publication Date: 7 January 2017
Cohort Profile
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English, were expected to deliver at the hospital and in-
tended to remain in Western Australia. A total of 2900
women (‘Generation 1’) were enrolled into the study.
There were 2868 live births–the index participants of
‘Generation 2’–including 60 sets of twins (n ¼ 120)
and two sets of triplets (n ¼ 6), from 2826 mothers (see
Figure 1).
The cohort has been regularly followed up since birth.
The number of participants has gradually decreased over
time (Figure 1) and the proportion of eligible participants
(those who have not died, withdrawn, been lost or
deferred) providing data at each assessment remained rela-
tively constant across childhood and adolescence, but has
reduced in young adulthood (Figure 2). The reduced par-
ticipation rate at the 2-year follow-up was due to the study
running out of resources to complete data collection of the
whole cohort.
Representativeness of the cohort
The representativeness and presence of potential biases in
the cohort have been examined with three sets of analyses.
Eligibility and consent rates at the recruiting clinics were
evaluated. Comparisons were made between the cohort
participants and the Western Australian population at
birth, childhood (year 8), adolescence (years 14 and 17)
and young adulthood (years 20 and 22). Comparisons
were also made between cohort participants and non-
participants for all follow-ups.
At the time of recruitment, to assess whether the Raine
Study cohort was representative of the population present-
ing at the recruitment sites, 6 months of clinic records in
the middle of the recruitment period were audited. In the
131 clinic sessions, 1420 women presented as new at-
tendees and 707 (50%) were eligible. Reasons for ineligi-
bility were: 36% were > 20 weeks’ gestation; 8% had
language difficulties; 4% planned to deliver elsewhere; and
2% had psychosocial problems precluding long-term
follow-up. Of the 707 eligible, 633 (90%) agreed to par-
ticipate during the audited period.
3
At birth, the characteristics of the Raine cohort were
compared with those of all live births (excluding Raine
births) in Western Australia during the 3-year recruitment
period, using data from the WA Department of Health
Midwives Notification System and Hospital Morbidity
Database. Comparisons were made of birthweight, gesta-
tion age, neonatal nursery admission, pregnancy complica-
tions, caesarean sections, maternal age, parity, marital
status and race. Overall, the characteristics of Raine par-
ticipants were similar to all Western Australian contem-
poraneous births except that Raine Study participants had
slightly more pregnancies with complications and caesar-
ean deliveries, and had more first-time mothers and un-
married mothers (see Table 1).
At the 8-year follow-up, the characteristics of partici-
pating cohort families were compared with the Year 2001
Western Australian Population Census data (see Table 2).
Demographic factors compared included family structure,
state of residence, parents’ place of birth, education, labour
force participation and occupational status, income level
and language spoken at home. Overall differences between
Raine Study and WA population families were small ex-
cept for more Raine parents residing in WA, being born
overseas, more with post-secondary and tertiary education
and in clerical/retail occupations, and less parents having
low incomes.
Year 1: Eligible 2819
Parcipated 2446
Year 2: Eligible 2787
Parcipated 1988
Year 3: Eligible 2757
Parcipated 2280
Year 5: Eligible 2711
Parcipated 2236
Deaths 28
Withdrawn 21
Lost/deferred 378
Deaths 2 (30)
Withdrawn 30 (51)
Lost/deferred 799
Deaths 0 (30)
Withdrawn 49 (79)
Lost/deferred 479
Deaths 0 (30)
Withdrawn 71 (198)
Lost/deferred 500
Post-birth
Livebirths: 2868
Year 10: Eligible 2490
Parcipated 2048
Year 14: Eligible 2424
Parcipated 1864
Year 17: Eligible 2352
Parcipated 1726
Year 20: Eligible 2313
Parcipated 1462
Year 8: Eligible 2490
Parcipated 2140
Year 22: Eligible 2262
Parcipated 1234
Deaths 2 (32)
Withdrawn 164 (412)
Lost/deferred 500
Deaths 0 (30)
Withdrawn 48 (127)
Lost/deferred 443
Deaths 0 (30)
Withdrawn 150 (348)
Lost/deferred 564
Deaths 4 (36)
Withdrawn 68 (480)
Lost/deferred 598
Deaths 1 (37)
Withdrawn 38 (518)
Lost/deferred 840
Deaths 4 (41)
Withdrawn 47 (565)
Lost/deferred 1029
Pre-birth
Fetus mothers
Enrolled: 2968
18 weeks: 2968
Miscarriages (GA<=23wks) 30
Terminaon of pregnancy 7
34 weeks: 2931
Withdrawn before birth 36
Sllborn 27
Figure 1. Flow diagram of Raine Study cohort participation.
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At the 14- and 17-year follow-ups, the cohort family
characteristics of participants were compared with Year
2006 Western Australian Population Census data of fami-
lies living in Western Australian with 15-17 year old chil-
dren, as this was the most appropriately representative
Western Australian demographic for comparison for either
follow-up (see Table 3). Demographic factors compared
included family structure, parents’ place of birth, educa-
tion, labour force and occupational status, income level
and an index of advantage/disadvantage. Overall, the char-
acteristics of the Raine families were similar to contempor-
aneous Western Australian families. There were no
substantial differences in proportions of family structure or
index of socioeconomic advantage/disadvantage. There
were more Raine families living in urban areas and with
tertiary education. At 14 years, there were more Raine par-
ents in clerical/administrative occupations and middle in-
comes, and at 17 these differences were reduced with a
shift of Raine parents to technical and professional occupa-
tions and higher incomes.
At the 20- and 22-year follow-ups, the characteristics of
cohort members participating in data collection were com-
pared with contemporaneous Year 2011 Western
Australian Census Data of 20- and 22-year-old males and
females living in Western Australia as the most appropri-
ately representative Western Australian demographic for
comparison (see Table 4; and Supplementary Tables 1 and
2, showing sex-specific comparisons, are available as
Supplementary data at IJE online). Demographic factors
compared included family structure, education completed,
labour force status, occupation, work hours and income
level. Overall, most comparisons showed the Raine cohort
had similar proportions as all Western Australian young
adults. Exceptions with more marked proportional differ-
ences (> 10%) indicated that the Raine cohort at 17 years
had more employed in clerical/retail, more working 40 or
more hours a week and more with higher incomes.
To assess any attrition bias, the characteristics at in-
fancy of participants and non-participants were compared
at each follow-up (see Tables 5, 6 and 7). In general, the
proportions of participants and non-participants across a
number of infant characteristics remained constant across
all follow-ups. An exception was a gradual reduction in
participation of infants of Aboriginal and Torres Strait
Islander ethnicity.
How often have they been followed up?
What has been measured?
The cohort has been assessed on 14 separate occasions.
Initial assessment was at 18 weeks gestation, and subse-
quent assessments were undertaken at 34 weeks, at birth
and at ages 1, 2, 3, 5, 8, 10, 14, 17, 18, 20 and 22 years.
Figure 2. Raine Study cohort participation rates across life-course periods.
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Currently assessment of participants at age 27 years is
under way.
Early assessments typically included primary and sec-
ondary caregiver reporting via questionnaire and clinical
assessments of the child participant. For the 14- and
17-year follow-ups, index participants provided self-
report information to complement caregiver reporting
and continued to perform clinical assessments. From the
18-year follow-up onwards, index participants provided
self-report information along with performing clinical as-
sessments. Specific assessments of reproduction were
undertaken in females at the 14-year follow-up and in
males at the 20-year follow-up. At the 18-year follow-up,
participants with mobility problems or a history of mental
health issues were not invited due to the social stressor
assessment.
Currently the database holds > 70 000 phenotypic
measures and > 20 million genetic variants on each partici-
pant, as well as over 170 000 biological samples in storage.
A list of measurements obtained at each follow-up is pre-
sented in Tables 8-11.
What has it found? Key findings and
publications
Since its genesis in 1989, over 400 peer-reviewed journal
papers have been published using the Raine Study data; a
full list is available on website [http://www.rainestudy.org.
au/research-findings/publications/], along with brief lay
Table 1. Comparison of Raine Study cohort families at birth
with the Western Australian (WA) population of babies born
contemporaneously, using linked data derived from the
Western Australian Department of Health Midwives
Notification System and Hospital Morbidity Database
Birth
Raine WA
n ¼ 2868 n ¼ 99 141
Mothers
Age (mean years) 27.5 27.7
Married (%) 82.1 89.4
Caucasian (%) 89.6 87.4
Parity (%)
0 48.1 39.0
1 28.7 32.7
2-3 20.6 24.5
4 2.5 3.8
Socioeconomic status:
IRSD
a
(mean) 1021 1022
Pregnancies
Complications (%) 38.6 30.0
Mode of delivery:
Spontaneous vertex 61.1 63.6
Breech 1.2 1.1
Instrumental 17.7 17.5
Caesarean section 21.1 18.9
Infants
Birthweight (g) 3283 3344
Birth length (cm) 48.8 49.9
Ponderal index (kg/m
3
) 27.9 26.7
Gestation (weeks) 39.0 39.1
Nursery admissions (%) 9.7 7.6
a
Index of Relative Soci-economic Disadvantage.
Table 2. Comparison of Raine Study cohort families at child-
hood (age 8 years) with contemporaneous Western
Australian (WA) Census population (2001 census data)
Age 8 follow-up
Raine WA
%%
Family structure
Single parent family 19.5 22.2
Couple family 80.5 77.8
Family state of residence
WA 84.3 74.6
Interstate 15.7 25.4
Parents’ place of birth
Australia ( 1 parent) 73.4 83.8
Overseas 26.6 16.2
Maternal education
a
Secondary 41.7 63.2
Post-secondary 36.3 15.3
Tertiary 19.7 9.1
Parent labour force/occupation
b
Professional/managerial 38.8 36.0
Clerical/retail 32.1 20.2
Technical/trade/labour 23.5 34.9
Not in labour force
c
5.6 8.8
Family income levels
d
Low 20.1 40.7
Medium 47.2 30.9
High 30.1 28.4
Language spoken at home
English 94.6 94.6
Other 5.4 5.4
a
Maternal education: WA 2001 Census data based on adult female educa-
tion levels; Raine data based on maternal education levels attained by 8 years.
b
Parent occupation: WA 2001 Census data based on 35-44 age category
for all persons to correspond to median maternal age and available paternal
age at 8 years [Raine: parent age median (interquartile range): maternal ¼
37.2 (33.1, 41.2); paternal ¼ 39.9 (36.2, 43.8)]; Raine data based on highest
level occupation of either parent at 8 years.
c
Not in labour force or not stated.
d
Family income: WA 2001 Census data based on weekly family income
for single and couple parent families: low, < $400 per week (pw); medium,
$400-$800 pw; high, > $800 pw; Raine family income level at 8 years: low,
< $25K per annum (pa); medium, $25K-$60K pa; high, > $60K pa.
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summaries of these papers [http://www.rainestudy.org.au/
research-findings/highlights/]. The publications used meas-
urements collected during the antenatal/perinatal, infancy,
childhood, adolescent and early adulthood periods.
Broadly, the nature of the measurements collected over the
years and used in these papers can be characterized as
being either: (i) genetic; (ii) phenotypic; (iii) behavioural;
(iv) environmental; or (iv) educational or work-related.
Obstetric
•
The randomized controlled trial demonstrated that a
protocol of five prenatal scans, compared with a single
mid-pregnancy morphology scan alone, does not prevent
preterm birth or improve pregnancy outcomes.
3
•
Follow-up to 8 years of age from the multiple and single
prenatal ultrasound groups provided strong evidence
that ultrasound imaging studies are safe,
4
as did follow-
up of eye structure and function at 20 years of age.
5
•
The unique serial fetal biometry measures have been
used to develop customized fetal growth charts.
6
Genetic
•
Genome-wide association studies have identified genetic
variants associated with fetal growth,
7
birthweight,
8
asthma,
9
obesity,
10
cognition
11
in childhood, vitamin D
levels in adolescence
12
and myopia in young
adulthood.
13
•
Exome array analysis has identified mutations in a num-
ber of genes associated with a later age of menarche.
14
•
Epigenetic studies have identified DNA methylation that
is related to adiposity in young adulthood.
15
Cardiometabolic
•
Maternal exposure to life stresses during pregnancy pre-
dicts increased weight but lower blood pressure in off-
spring at 20 years of age.
16
Table 3. Comparison of Raine Study cohort families at ado-
lescence (ages 14 and 17 years) with contemporaneous
Western Australian (WA) Census population (2006 Census
data)
Age 14 follow-up Age 17 follow-up
Raine WA Raine WA
%%%%
Family structure
Single parent family 23 24 22 24
Couple family 77 76 78 76
Family area of residence
Rural 22 34 18 34
Urban 78 66 82 66
Family socioeconomic status
a
Lowest tertile 3.0 3.0 3.5 5.0
Middle tertile 78.5 80.0 83.5 83.5
Highest tertile 18.5 17.0 13.0 11.0
Parent place of birth
Australia ( 1 parent) 70.9 69.5 69.5 69.5
Overseas 29.1 30.5 30.4 30.5
Parent education
Secondary 50.8 49.6 48.9 49.6
Post-secondary 27.6 32.6 28.7 32.6
Tertiary 21.7 17.8 22.5 17.8
Parent labour force/occupation
Professional/managerial
b
35.3 33.4 42.1 33.4
Clerical/retail
b
34.8 24.7 25.9 24.7
Technical/trade/labour
b
14.2 23.6 20.1 23.6
Not in labour force
c
15.8 18.3 11.7 18.3
Parent income levels
Low 13 11 8 11
Medium 69 55 58 55
High 18 34 34 34
a
Index of Relative Socioeconomic Advantage and Disadvantage.
b
Out of % in labour force.
c
By choice.
Table 4. Comparison of Raine Study cohort participants at
young adulthood (ages 20 and 22 years) with contemporan-
eous Western Australian (WA) Census population (2011
Census data)
Age 20 follow-up Age 22 follow-up
Raine WA Raine WA
%%%%
Family structure
Not married 88.5 87.4 77.7 78
De facto married 11.6 12.7 22.4 22
Any children 4.3 1.2 7.5 2.6
Education completed
Secondary > year 10 88.1 83.2 88.4 83.2
Post-secondary/ ¼
tertiary study
21.5 27.0 40.2 46.5
Labour force/occupation
Professional/managerial
a
4.2 8.2 16.8 17.9
Clerical/retail
a
56.0 49.8 54.3 41.5
Technical/trade/ labour
a
39.6 40.6 29.4 39.3
Unemployed/not
in labour force
19.2 26.6 17.5 23.7
Work hours per week
< 40 66.6 73.5 55.9 65.2
40þ 33.5 26.6 44.2 34.9
Income levels
Low 18.5 18.5 44.3 52.0
Medium 46.4 43 32.7 35.5
High 35.2 38.5 23.1 12.6
a
Out of total n employed in labour force.
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