Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000037606
Ethics application status
Approved
Date submitted
18/12/2022
Date registered
13/01/2023
Date last updated
13/01/2023
Date data sharing statement initially provided
13/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Maternal metabolic health And Mother and Baby health Outcomes (MAMBO): An observational cohort study
Scientific title
Maternal metabolic health And Mother and Baby health Outcomes (MAMBO): An observational cohort study
Secondary ID [1] 308738 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MAMBO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Large for gestational age (LGA) 328525 0
Dysglycaemia 328526 0
Small for gestational age (SGA) 328564 0
Obesity 328565 0
Hypertension 328566 0
Condition category
Condition code
Reproductive Health and Childbirth 325543 325543 0 0
Complications of newborn
Metabolic and Endocrine 325580 325580 0 0
Other metabolic disorders
Metabolic and Endocrine 325581 325581 0 0
Diabetes
Diet and Nutrition 325582 325582 0 0
Obesity

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Women will be recruited to the MAMBO study when they attend maternity care visits at The Women’s or Frances Perry House prior to 20±4 completed weeks gestation. The initial contact will be made by the maternity care provider. Subsequent contact will be made by a dedicated trial nurse at the time of the standard maternity care visit. Written consent will be obtained.

To facilitate long-term follow-up of the MAMBO cohort, we are collaborating with Generation Victoria (GenV: https://genv.org.au). GenV is aiming to recruit parallel cohorts of newborns and their parents (estimated 160,000) in the state of Victoria (population 6.5 million), Australia, over two full years from October 2021. Its goal is to generate translatable evidence (prediction, prevention, treatments, services and policy) to improve the future wellbeing of all children and adults and to reduce future disease burden. Importantly, the GenV cohort only recruits parents and offspring after birth and will follow the child and parent/s indefinitely until the study closes (no end date set at this point) or withdrawal. GenV conducts retrospective and prospective linkage to clinical and administrative datasets and banking of retrospective and prospective clinical and GenV specific biosamples for the GenV cohorts.

Women will be informed about the Gen V study when they are recruited to the MAMBO study. They can make the decision whether or not they wish to participate in Gen V after the birth of their baby.

For the MAMBO study, the first clinical trial visit can occur the same day as the consent or within 4 weeks of recruitment, provided that the initial visit occurs before 24 completed weeks gestation. All MAMBO participants will be given information about GenV and asked whether 1) they consent to MAMBO sharing their contact details with GenV, ie so that MAMBO and GenV are aware of who is participating in both studies and GenV can contact MAMBO participants for recruitment to GenV and 2) they consent to MAMBO and GenV sharing information between the two studies. This optional data sharing consent will only apply to participants who are enrolled in both studies.

Study Visits:
First study visit: The study visit will occur at 20 weeks on the day of recruitment or within 4 weeks of recruitment. To minimize the burden on women, this could occur on the same day as the consent. The GenV study will be discussed with participants but recruitment to GenV will only occur after delivery. Study activities include:
• Documentation of maternal and (if available) paternal demographic details
• Collect medical history and medication history from the electronic medical record
• Maternal anthropometry: Height, weight, waist circumference, bioimpedance, blood pressure
• Collection of blood (non-fasting): Glucose, lipids, leptin, CRP, c-peptide, insulin.

Second study visit: The second study visit will occur at 36 weeks gestation ±4 weeks gestation. At this visit, subjects will be provided with a kit to collect maternal and baby mouth swabs within a few days of delivery. Study activities include:
• Collect medical history and medication history from the electronic medical record (including GTT, and maternity ultrasound results)
• Ultrasound data: Estimated fetal weight and abdominal circumference on all available obstetric ultrasounds that have been formally reported and appear in the electronic medical record.
• Maternal anthropometry: Height, waist circumference, bioimpedance, blood pressure
• Collection of blood (non-fasting): Glucose, lipids, leptin, CRP, c-peptide, insulin.

Data Collection Visit (peripartum):
• Cheek swab (for epigenetic analysis) will be taken from mother and baby according to the protocol. These samples will be self-collected before discharge from hospital using a kit supplied at 36 weeks gestation. Samples will be given to nursing staff and will be sent to pathology for long-term storage until all samples are collected.
• Collection of history discharge summary which includes the birth record.

Third study visit: The third study visit will occur at 12-18 months post-delivery. Study activities include:
• Collect medical history and medication history from the electronic medical record and/or patient
• Maternal anthropometry: Height, weight, waist circumference, bioimpedance, blood pressure
• Collection of blood (non-fasting): Glucose, lipids, leptin, CRP, c-peptide, insulin.
• Weight and height of children as recorded in the childhood development book (‘Baby book’)
• Neonatal anthropometry: Weight, length, abdominal circumference, body composition (using mid-arm circumference and triceps skinfold)(18)

In order to encourage attendance at this visit, parking and meal vouchers will be provided. Women will be provided with a comprehensive summary of their metabolic health and a plan for appropriate long-term follow-up. The Gen V team will have regular contact with participants between 0 and 12-18 months and will encourage women to attend the 12-18 month visit. If a face-to-face visit is not possible, a phone visit will be deemed acceptable.



Intervention code [1] 325107 0
Diagnosis / Prognosis
Intervention code [2] 325116 0
Early Detection / Screening
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333409 0
A composite of LGA (birthweight >90th centile) and SGA (birthweight <10th centile).

Birthweight will be taken from the medical record. It is measured on calibrating digital scales (to the nearest 1g) immediately post-delivery.
Timepoint [1] 333409 0
Birth (0 days of life)
Secondary outcome [1] 416945 0
A composite of dysglycaemia outcomes will be measured using either a fasting plasma glucose, HbA1c or 75g oral glucose tolerance test (OGTT) and will include:
- Gestational Diabetes as per International Association of Diabetes in Pregnancy Study Group (IADPSG) definition (75g OGTT results of Fasting equal or greater than 5.1mmol/L, one-hour equal or greater than 10.0mmol/L, two-hour equal or greater than 8.5mmol/L)
- Overt diabetes in pregnancy or in the post-partum period (Fasting glucose equal or greater than 7.0mmol/L or random glucose equal or greater than 11.1mmol/L) or HbA1c equal or greater than 6.5%
- Prediabetes in the post-partum period as defined by the Australian Diabetes Society position statement (HbA1c equal or greater than 6.0% or Fasting glucose equal or greater than 6.0mmol/L or 2hr post-prandial or random glucose equal or greater than 7.8mmol/L)

Timepoint [1] 416945 0
At clinical trial visits (20 plus or minus 4 weeks, 36 plus or minus, delivery, 12-18 months post-partum) or as recorded in the medical record.
Secondary outcome [2] 416946 0
A composite of hypertension outcomes as measured by:
- The development of gestational hypertension as defined by a blood pressure measured using a sphygmomanometer of equal to or greater than 140/90mmHg on two occasions or as recorded n the medical record.
- The use of blood pressure medication in pregnancy for the treatment of hypertension.
- The development of NEW hypertension in the post-partum period as defined by a blood pressure measured using a sphygmomanometer of equal to or greater than 140/90mmHg on two occasions or as recorded n the medical record.
- The use of blood pressure medication in the post-partum period for the treatment of NEW hypertension.
The development of gestational hypertension or hypertension after pregnancy (equal to or greater than 140/90mmHg or use of anti-hypertensive medication)
Timepoint [2] 416946 0
At clinical trial visits (20 plus or minus 4 weeks, 36 plus or minus, delivery, 12-18 months post-partum) or as recorded in the medical record.
Secondary outcome [3] 416947 0
A composite of body weight outcomes including:
- Gestational weight gain equal to or greater than 20kg (as measured by calibrated digital scales to the nearest 0.1kg)
- NEW overweight/obesity after pregnancy (BMI equal to or greater than 25kg/m2 and body weight increase of equal to or greater than 5kg compared with pre-pregnancy weight) with weight measured by calibrated digital scales (to the nearest 0.1kg and height measured by stadiometer to the nearest 1cm)
Timepoint [3] 416947 0
At clinical trial visits (20 plus or minus 4 weeks, 36 plus or minus, delivery, 12-18 months post-partum) or as recorded in the medical record.
Secondary outcome [4] 416948 0
A composite of the above secondary outcomes.
- Gestational Diabetes as per International Association of Diabetes in Pregnancy Study Group (IADPSG) definition (75g OGTT results of Fasting equal or greater than 5.1mmol/L, one-hour equal or greater than 10.0mmol/L, two-hour equal or greater than 8.5mmol/L)
- Overt diabetes in pregnancy or in the post-partum period (Fasting glucose equal or greater than 7.0mmol/L or random glucose equal or greater than 11.1mmol/L) or HbA1c equal or greater than 6.5%
- Prediabetes in the post-partum period as defined by the Australian Diabetes Society position statement (HbA1c equal or greater than 6.0% or Fasting glucose equal or greater than 6.0mmol/L or 2hr post-prandial or random glucose equal or greater than 7.8mmol/L)
Gestational weight gain equal to or greater than 20kg (as measured by calibrated digital scales to the nearest 0.1kg)
- NEW overweight/obesity after pregnancy (BMI equal to or greater than 25kg/m2 and body weight increase of equal to or greater than 5kg compared with pre-pregnancy weight) with weight measured by calibrated digital scales (to the nearest 0.1kg and height measured by stadiometer to the nearest 1cm)
- Gestational weight gain equal to or greater than 20kg (as measured by calibrated digital scales to the nearest 0.1kg)
- NEW overweight/obesity after pregnancy (BMI equal to or greater than 25kg/m2 and body weight increase of equal to or greater than 5kg compared with pre-pregnancy weight) with weight measured by calibrated digital scales (to the nearest 0.1kg and height measured by stadiometer to the nearest 1cm)
Timepoint [4] 416948 0
At clinical trial visits (20 plus or minus 4 weeks, 36 plus or minus, delivery, 12-18 months post-partum) or as recorded in the medical record.


Eligibility
Key inclusion criteria
Eligibility for the study will be women with pregnancies <20±4 completed weeks of gestation who provide written consent. The study will include all women including those with multifetal pregnancies, chronic disease, and those using medications of any type. Women from non-English speaking backgrounds will be included and telephone interpreting services will be used as required.
Minimum age
16 Years
Maximum age
55 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
The only exclusion criterion is the incapacity for the woman to understand the requirements of her participation. This may be due to illiteracy, intellectual disability or a severe active mental illness. It is anticipated that less than 1/1000 women screened at Royal Women's Hospital or Frances Perry Hospital would fulfil this criterion.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Summary characteristics of the study cohort will be described using means (with standard deviations) or medians (with interquartile ranges) for continuous variables, depending on the shape of the distribution, and numbers and percentages for categorical variables. Summary statistics for the outcome of interest (LGA/SGA offspring). It will also be provided for the whole group obesity (maternal BMI equal to or greater than 30kg/m2) and for obesity classes (Class 1 obesity BMI 30-34.9kg/m2; Class II obesity BMI 35-39.9kg/m2; Class III obesity BMI equal to or greater than 40.0kg/m2). It will be provided for whole diabetes (Y/N) and based on HbA1c in the third trimester (equal to or less than 5.5%, 5.6-7.5%, equal to or greater than 7.5%). It will be provided for whole group hypertension (Y/N) and based on hypertension class or number of anti-hypertensive agents used (Prehypertension equal to or less than 139/89mmHg, Grade 1 equal to or less than 159/99mmHg or 1 agent, Grade 2 equal to or greater than 160/100 or more than 1 agent).

Development of the predictive model: A predictive model for delivery of LGA offspring in obese women will be derived using data collected. Logistic regression analysis will be conducted to identify candidate predicators. After starting with the most comprehensive model that includes all potential risk factors (e.g., presence of pre-existing diabetes or gestational diabetes, previous LGA/SGA delivery, parity), a backward selection method will be performed to determine which combination of risk factors generates the most parsimonious predictive model. The number of candidate variables will be limited to data collected in the dataset. From this parsimonious model, model coefficients and the associated 95% confidence intervals (CI) will be extracted to derive the risk score for predicting the delivery of LGA/SGA offspring.

Internal validation: The final multivariable prediction model will be internally validated using bootstrapping (1,000 replications). Optimism in performance of the model, due to overfitting, will be estimated as the average of the difference in performance of the model in bootstrap sample and original dataset. The optimism then subtracted from the original performance measure (C-statistic of the original model) to provide optimism-corrected C-statistic of the final model. Shrinkage factor will be estimated as the percentage of the difference between C-statistics of the original model and the optimism-corrected C-statistics. Coefficients from the multivariable logistic regression will be multiplied by the shrinkage factor to recalibrate the final model allowing for more reliable predictions.

Ongoing statistical input will be provided by MISCH (Methods and Implementation Support for Clinical and Health research) at the University of Melbourne in collaboration with the statistics team supporting GenV.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/02/2023
Actual
Date of last participant enrolment
Anticipated
30/12/2023
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23735 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 23736 0
Frances Perry House - Parkville
Recruitment postcode(s) [1] 39176 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 312864 0
Government body
Name [1] 312864 0
National Health and Medical Research Council
Country [1] 312864 0
Australia
Funding source category [2] 312876 0
Charities/Societies/Foundations
Name [2] 312876 0
Ramsay Hospital Research Foundation
Country [2] 312876 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Grattan St
Parkville, VIC 3010
Country
Australia
Secondary sponsor category [1] 314524 0
None
Name [1] 314524 0
Address [1] 314524 0
Country [1] 314524 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312141 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 312141 0
Ethics committee country [1] 312141 0
Australia
Date submitted for ethics approval [1] 312141 0
10/10/2022
Approval date [1] 312141 0
17/11/2022
Ethics approval number [1] 312141 0
HREC/90080/MH-2022

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123626 0
Dr Sarah Price
Address 123626 0
Department of Obstetric Medicine
Royal Women's Hospital
20 Flemington Rd
Parkville, VIC 3052
Country 123626 0
Australia
Phone 123626 0
+61 3 8345 2162
Fax 123626 0
Email 123626 0
[email protected]
Contact person for public queries
Name 123627 0
Sarah Price
Address 123627 0
Department of Obstetric Medicine
Royal Women's Hospital
20 Flemington Rd
Parkville, VIC 3052
Country 123627 0
Australia
Phone 123627 0
+61 3 8345 2162
Fax 123627 0
Email 123627 0
[email protected]
Contact person for scientific queries
Name 123628 0
Sarah Price
Address 123628 0
Department of Obstetric Medicine
Royal Women's Hospital
20 Flemington Rd
Parkville, VIC 3052
Country 123628 0
Australia
Phone 123628 0
+61 3 8345 2162
Fax 123628 0
Email 123628 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All IPD will be shared after publication.
When will data be available (start and end dates)?
Data for trial design will be available after publication (Anticipated MAY 2023). Data will be available until 5 years after the final publication.
Available to whom?
Available to researchers and clinicians by email request to the principal investigator for the purposes of research and other academic work. Data will be available via email request to: [email protected].
Available for what types of analyses?
For the aims in the approval proposal.
How or where can data be obtained?
Data will be made available by email request to: [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17914Study protocol  [email protected]
17915Statistical analysis plan  [email protected]
17916Informed consent form  [email protected]
17917Ethical approval  [email protected]



Results publications and other study-related documents

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