ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12621001173886

Ethics application status

Approved

Date submitted

28/06/2021

Date registered

31/08/2021

Date last updated

19/09/2022

Date data sharing statement initially provided

31/08/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

A NEW ZEALAND VERY LOW BIRTHWEIGHT STUDY PROJECT: Cardiovascular Outcomes for Mothers and Babies. Hauora Manawa Mo Nga Whanau.

Scientific title

Intergenerational risk of cardiovascular disease in adults born prematurely and mothers who give birth prematurely: A New Zealand Very Low Birth Weight Longitudinal Cohort Study Project.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

NZVLBW-COMB

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Cardiovascular disease

Premature birth

Very low birth weight

Condition category

Condition code

Cardiovascular

Hypertension

Metabolic and Endocrine

Diabetes

Diet and Nutrition

Obesity

Cardiovascular

Coronary heart disease

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

This observational study is part of an ongoing longitudinal cohort study investigating outcomes after premature birth at < 1500g. For this project, focusing on cardiovascular health, we will be looking at two generations (mothers who delivered a baby prematurely weighing < 1500g in 1986 and these very low birth weight offspring)

Exposure:
1. Premature birth at < 37 weeks gestation and birth weight < 1500g in New Zealand in 1986 (offspring study)
2. Delivery of a baby at <37 weeks and weighing < 1500g in New Zealand in 1986 (maternal study)

Intervention code [1]

Not applicable

Comparator / control treatment

Control groups:
1. Same age peer control group born at term at a healthy birth weight in New Zealand in 1986 (offspring study)
2. Women who delivered a baby at term at a healthy birth weight in New Zealand in 1986 (maternal study) - these are the mothers of the control group above

Control group

Active

Outcomes

Primary outcome [1]

Cardiovascular disease events ( ischaemic heart disease, heart failure, cerebrovascular disease or death secondary to these events) as a composite outcome. This will be identified by review of health records.

Timepoint [1]

1. Events that have occurred up to 36 years of age for offspring study
2. Events that have occurred up to 36 years after giving birth to a very low birth weight baby for maternal study

Primary outcome [2]

Ischaemic heart disease (identified by review of medical records).

Timepoint [2]

1. Events that have occurred up to 36 years of age for offspring study
2. Events that have occurred up to 36 years after giving birth to a very low birth weight baby for maternal study

Primary outcome [3]

Heart failure (identified by review of medical records).

Timepoint [3]

1. Events that have occurred up to 36 years of age for offspring study
2. Events that have occurred up to 36 years after giving birth to a very low birth weight baby for maternal study

Secondary outcome [1]

Hypertension - blood pressure measured by a sphymomanometer and hypertension defined using 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline Definition:
Normal BP is systolic less than 120 mmHg, and diastolic less than< 80 mm Hg;
Elevated BP is systolic 120-129 mmHg, and diastolic less than 80 mm Hg;
Hypertension stage 1 is systolic 130-139 mmHg or diastolic 80-89 mm Hg,
Hypertension stage 2 is systolic greater than or equal to 140 mmHg or diastolic greater than or equal to 90 mm Hg.

Timepoint [1]

1. offspring study :35-36 years of age
2.maternal study: 35-36 years after giving birth to a very low birth weight baby

Secondary outcome [2]

Diabetes mellitus defined as: previously confirmed diagnosis or HbA1C greater than or equal to 50 mmol/mol (collected by blood sample)

Timepoint [2]

1. offspring study :up to 35-36 years of age
2.maternal study: up to 35-36 years after giving birth to a very low birth weight baby

Secondary outcome [3]

Impaired glucose tolerance (pre-diabetes) defined as: HbA1C 41 - 49 mmol/mol (collected by blood sample)

Timepoint [3]

1. offspring study : up to 35- 36 years of age
2.maternal study: up to 35- 36 years after giving birth to a very low birth weight baby

Secondary outcome [4]

Unhealthy weight. Weight will be measured on a scale and height on a stadiometer or using a tape measure. Unhealthy weight defined as:
1. Body mass index greater than 25 "overweight", greater than 30 "obese" or
2. By health risk category (moderate or high)for the waist to hip ratio (measured using a paper tape).
Women: moderate risk equals 0.81-0.85, high risk is greater than or equal to 0.86.
Men: moderate risk equals 0.96-1.0, high risk is greater than or equal to 1.0

Timepoint [4]

1. offspring study :35-36 years of age
2.maternal study: 35-36 years after giving birth to a very low birth weight baby

Secondary outcome [5]

Unhealthy lipid profile assessed using a blood sample and defined as:
total cholesterol greater than or equal to 4 mmol/L
LDL cholesterol greater than or equal to 1.8 mmol/L
HDL cholesterol less than or equal to 1 mmol/L
triglycerides greater than or equal to 1.7 mmol/L
total chol/HDL ratio less than or equal to 4.

Timepoint [5]

1. offspring study :up to 35-36 years of age
2.maternal study: up to 35-36 years after giving birth to a very low birth weight baby

Secondary outcome [6]

Five year predicted risk of cardiovascular disease based on validated risk calculator (NZ Primary Prevention Equations.)

Timepoint [6]

Calculated at:
Offspring study: 26-30 years after being born very low birth weight
Maternal study: 35-36 years after giving birth to a very low birth weight infant.
For the offspring study this risk prediction based on assessments done at 26-30 years will be compared to actual events up to 35-36 years of age.
For the maternal study this risk prediction will form a baseline risk prediction for a future follow-up study.

Secondary outcome [7]

Cerebrovascular disease (identified by review of medical records) as a primary outcome.

Timepoint [7]

1. Events that have occurred up to 36 years of age for offspring study
2. Events that have occurred up to 36 years after giving birth to a very low birth weight baby for maternal study

Secondary outcome [8]

Reproductive health (Women only). This will be identified through self-report by participant questionnaire (questions written specifically for this study) and confirmed where possible against medical records.
This will include:
- fertility assistance to conceive
- pregnancy losses
- live births
- complications of pregnancy (multiple pregnancy, gestational diabetes, preeclampsia/hypertension, preterm delivery)
- onset of menopause

Timepoint [8]

1. offspring study :35-36 years of age
2.maternal study: 35-36 years after giving birth to a very low birth weight baby

Secondary outcome [9]

Kidney function. This will be measured through a blood sample for creatinine and then using this creatinine level, glomerular filtration rate will be estimated using the Chronic Kidney Disease Epidemiological Collaboration equation.

Timepoint [9]

1. offspring study :26-30 years of age (Collected as part of previous data collection)
2.maternal study: 35-36 years after giving birth to a very low birth weight baby

Secondary outcome [10]

General health and health service utilisation : This will be determined by self-report by participant health questionnaire and cross-checked against medical records where possible. These outcomes will include:
- chronic medical conditions
-neurodisability
- dental health
- hospitalisations over the past 12 months
- family doctor visits over the past 12 months
- specialist outpatient appointments over the last 12 months
- self-perception of health and well-being
- diet and exercise
These questions have been written specifically for this study with the exceptions below.

The self-perception of health and well-being questions were sourced from:
1. Perceived stress scale (Cohen, S., Kamarck, T., & Mermelstein, R. (1983). A global measure of perceived stress. Journal of Health and Social Behavior, 24, 385-396.)
2. The ABCD Risk Questionnaire (Woringer M, Nielsen JJ, Zibarras L, et al. Development of a questionnaire to evaluate patients’ awareness of cardiovascular disease risk in England’s National Health Service Health Check preventive cardiovascular programme. BMJ Open 2017;7:e014413. doi:10.1136/ bmjopen-2016-014413 )
3, University of Rhode Island Change Assessment Scale (URICA) (DiClemente, C.C. & Hughes, S.O. (1990). Stages of change profiles in alcoholism treatment. Journal of Substance Abuse, 2, 217-235. )
4. The New Zealand Health Survey. (Ministry of Health. 2020. Content Guide 2019/20: New Zealand Health Survey. Wellington: Ministry of Health. ISBN:978-1-99-002966-0 )

The diet questions were sourced from:
The New Zealand Health Survey. (Ministry of Health. 2020. Content Guide 2019/20: New Zealand Health Survey. Wellington: Ministry of Health. ISBN:978-1-99-002966-0)

The exercise questions were sourced from:
INTERNATIONAL PHYSICAL ACTIVITY QUESTIONNAIRE (LONG LAST 7 DAYS SELF-ADMINISTERED version of the IPAQ. Revised October 2002.) (Booth, M.L. (2000). Assessment of Physical Activity: An International Perspective. Research Quarterly for Exercise and Sport, 71 (2): s114-20)

Timepoint [10]

1. offspring study :35-36 years of age
2.maternal study: 35-36 years after giving birth to a very low birth weight baby

Secondary outcome [11]

Mental health. This will be assessed by self-report of mental health diagnoses by participant health questionnaire. These questions were specifically written for this study.

Timepoint [11]

1. offspring study :35-36 years of age
2.maternal study: 35-36 years after giving birth to a very low birth weight baby

Eligibility

Key inclusion criteria

1. Participants in the population-based New Zealand Very Low Birth Weight Cohort who were born in New Zealand in 1986 at < 37 weeks gestation and weighing <1500g (offspring study)
2. Mothers of participants in the New Zealand Very Low Birth Weight Cohort Study

Minimum age

34 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Decline participation.
For control group: Not born in New Zealand in 1986, not born at full term, born small for gestational age, not healthy at birth

Study design

Purpose

Natural history

Duration

Longitudinal

Selection

Defined population

Timing

Both

Statistical methods / analysis

At previous data collection waves for the NZ Very Low Birth Weight (VLBW) Study we have retained ~ 250 VLBW participants and 100 controls. For comparisons of adult cardiovascular risk in the NZVLBW cohort vs controls and between their mothers vs control mothers, the study has 80% power at a=.05 to detect a mean effect size difference in outcome (eg mean heart age, mean %age likelihood of heart attack in next 5 years) in excess of 0.35 SD. These estimates suggest that the study has adequate power to detect small to moderate effect size differences in comparisons of interest.
The cardiovascular disease event rate and the incidence of cardiovascular risk factors will be compared between:
1. VLBW group and controls
2. Mothers who delivered a VLBW baby and to mothers of controls
The cardiovascular disease event rate will then be adjusted for cardiovascular risk factors, gender and age in order to determine the relative contribution of premature birth/premature delivery alone to any between-group differences.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

6/09/2021

Actual

16/09/2021

Date of last participant enrolment

Anticipated

31/12/2023

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

700

Accrual to date

100

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Country [2]

United Kingdom

State/province [2]

Country [3]

United States of America

State/province [3]

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Heart Foundation of New Zealand

Address [1]

PO Box 17160, Greenlane, Auckland 1546

Country [1]

New Zealand

Funding source category [2]

Charities/Societies/Foundations

Name [2]

Maurice and Phyllis Paykel Trust

Address [2]

PO Box 110008
Auckland Hospital
Auckland 1148

Country [2]

New Zealand

Funding source category [3]

Charities/Societies/Foundations

Name [3]

Cure Kids New Zealand

Address [3]

PO Box 90 907 Victoria Street West Auckland 1142

Country [3]

New Zealand

Funding source category [4]

Charities/Societies/Foundations

Name [4]

Christchurch Heart Institute Trust

Address [4]

University of Otago Christchurch
PO Box 4345
Christchurch 8140

Country [4]

New Zealand

Primary sponsor type

University

Name

University of Otago

Address

Centre for Innovation, Level 1 (East Wing), 87 St David St, Dunedin

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern B New Zealand Health and Disability Ethics Committee

Ethics committee address [1]

Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140

Street address:
133 Molesworth Street
Thorndon
Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

26/05/2021

Approval date [1]

04/06/2021

Ethics approval number [1]

21/NTB/145

Summary

Brief summary

Adults who were born prematurely and mothers who give birth to a preterm baby are at increased risk of cardiovascular disease but neither are included in New Zealand’s risk assessment guidelines. As part of a wider project investigating the impact of premature birth on cardiovascular health we will invite the New Zealand Very Low Birth Weight cohort (born <1500g) and their mothers to have their cardiovascular disease risk assessed and compared to a control group. We will compare cardiovascular risk factors, cardiovascular events, general health and reproductive history  in the premature-born NZ VLBW cohort and controls at age 35 years (2021). Cardiovascular events and risk factor trajectory will be compared to cardiovascular risk estimations using health data collected as part of  risk factor data collected at 28 years of age using validated calculators (such as NZ PREDICT guidelines). We will also compare cardiovascular disease event rate and all-cause mortality in mothers of the NZ VLBW cohort compared to mothers of controls and calculate and compare five year cardiovascular risk estimates using the NZ PREDICT equations.  This will be compared to actual cardiovascular disease events as part of a comprehensive evaluation of cardiovascular health planned in five years’ time. Evaluation for cardiovascular risk in participants will be based upon medical history, blood pressure and anthropometric measurements and blood testing for diabetes and dyslipidemia. This study and our wider research project will help to inform recommendations around cardiovascular risk screening after preterm birth/delivery.

Trial website

https://www.otago.ac.nz/christchurch/departments/paediatrics/otago040041.html

Trial related presentations / publications

Public notes

Our cardiovascular risk trajectory begins in the womb. 7.5% of New Zealand babies are born
prematurely (< 37 weeks gestation). Most now survive to adulthood. However, there is increasing evidence that premature babies and their mothers are at increased risk of a premature death due to potentially preventable cardiovascular diseases. Current national guidelines for the cardiovascular disease risk assessment do not include premature birth as a risk factor which may mean they are inadequate to protect these groups.
Our project aims to:
1.  Compare cardiovascular risk/disease in a national cohort of adults born prematurely to a
healthy term-born peer group
2. Compare cardiovascular risk /disease in the mothers of this cohort who birthed prematurely to mothers who birthed at term

Contacts

Principal investigator

Name

Dr Sarah Harris

Address

Department of Paediatrics
University of Otago Christchurch
PO Box 4345
Christchurch 8140

Country

New Zealand

Phone

+64 3 3726725

Fax

sarah.harris@otago.ac.nz

Contact person for public queries

Name

Sarah Harris

Address

Department of Paediatrics
University of Otago Christchurch
PO Box 4345
Christchurch 8140

Country

New Zealand

Phone

+64 3 3726725

Fax

sarah.harris@otago.ac.nz

Contact person for scientific queries

Name

Sarah Harris

Address

Department of Paediatrics
University of Otago Christchurch
PO Box 4345
Christchurch 8140

Country

New Zealand

Phone

+64 3 3726725

Fax

sarah.harris@otago.ac.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Deidentified individual participant data from this trial (where consent has been given to share data with other research groups) after these data have been published by our group.

When will data be available (start and end dates)?

At the end of our trial but only after all of our study results have been published in peer-reviewed journal.

Available to whom?

Adults Born Preterm International Collaboration

Available for what types of analyses?

IPD- meta-analysis

How or where can data be obtained?

Requests for use of data would need to be evaluated by the study team and principal investigator sarah.harris@otago.ac.nz. Data-sharing will only occur if the request meets ethical approval requirements and only deidentified data would be shared. A formal data-sharing contract would need to be negotiated that includes ethical considerations and provisions for data protection and integrity.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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