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Trial registered on ANZCTR


Registration number
ACTRN12617001082392
Ethics application status
Approved
Date submitted
14/07/2017
Date registered
26/07/2017
Date last updated
26/07/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Investigating the risk of adverse maternal and infant perinatal outcomes following vaccination during pregnancy, Australia 1994-2015.
Scientific title
Retrospective cohort analysis to investigate the risk of adverse maternal and infant perinatal outcomes following vaccination during pregnancy, Australia 1994-2015.
Secondary ID [1] 292435 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
FluMum study: ACTRN12612000175875
PneuMum study: NCT00310349

Health condition
Health condition(s) or problem(s) studied:
Maternal vaccination 304032 0
Respiratory illnesses 304035 0
Pregnancy 304036 0
Condition category
Condition code
Public Health 303359 303359 0 0
Epidemiology
Reproductive Health and Childbirth 303360 303360 0 0
Fetal medicine and complications of pregnancy
Infection 303361 303361 0 0
Other infectious diseases
Reproductive Health and Childbirth 303362 303362 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 303363 303363 0 0
Normal pregnancy

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Retrospective cohort analyses of four separate datasets where data collection is complete.
Written, informed consent was obtained from each individual participant in each study.
1. 'FluMum' (NHMRC Project Grant no.APP1020035, HREC Reference Number: 2012-1744) . Data collection occurred from 01 April 2012- 30 June 2015.
2.'PneuMum' (HREC Reference Number: 05-52). Data collection occurred from August 2006 and January 2011. Exact dates of data collection not provided due to potentially identifiable information of Indigenous participants.
3. '1+1HS' (HREC Reference Number: 2016-2710) studies. Data collection occurred from 2004-2006 and 2009-2011. Exact dates of data collection not provided due to potentially identifiable information of Indigenous participants.
Participants were interviewed by trained research staff using a detailed structured questionnaire at birth and then at 6 months post-partum.
Exposures will be inactivated influenza, dTpa(pertussis) and 23v polysaccharide pneumococcal vaccines in pregnancy compared to unvaccinated pregnant women.
Intervention code [1] 298608 0
Not applicable
Comparator / control treatment
Historical NT birth cohort of de-identified perinatal data from 1 Jan 1984-31 Dec 2014 based on an NHMRC funded probabilistically linked study 'Partnership Project Grant'
HREC Reference number: 2017-2749.
Control group
Historical

Outcomes
Primary outcome [1] 302753 0
Congenital anomalies between infants of vaccinated and unvaccinated mothers up until 6 months post-partum as assessed by maternal self-report and medical record review. For international consistency, congenital anomalies will be identified using ICD-10 coding and will be classified according to the Brighton Collaboration working group definitions.
Timepoint [1] 302753 0
up until 6 months post-partum.
Primary outcome [2] 302768 0
low birthweight in infants of vaccinated and unvaccinated mothers as assessed by maternal self-report and medical record review. For our study, low birthweight is defined as an infant at term weighing less than 2500grams.
Timepoint [2] 302768 0
up until 6 months post-partum
Primary outcome [3] 302769 0
preterm birth in infants of vaccinated and unvaccinated mothers as assessed by maternal self-report and medical record review. For our study preterm birth will be define as less than 37 completed weeks gestation.
Timepoint [3] 302769 0
up until 6 months post-partum
Secondary outcome [1] 336906 0
PRIMARY OUTCOME=Small for gestational age (SGA) in infants of vaccinated and unvaccinated mothers assessed by calculation using validated algorithm of infant birthweights and gestations at birth (self-reported and medical record review). Our study defines SGA as birth weight below the 10th percentile of the Australian population birth weight versus gestational age greater than or equal to 20 weeks gestation, by sex.
Timepoint [1] 336906 0
up until 6 months post-partum
Secondary outcome [2] 337010 0
PRIMARY OUTCOME=Maternal deaths as assessed by medical record review
Timepoint [2] 337010 0
up until 6 months post-partum
Secondary outcome [3] 337011 0
PRIMARY OUTCOME=All cause maternal hospitalisations as assessed by maternal self-report and medical record review
Timepoint [3] 337011 0
up until 6 months post-partum
Secondary outcome [4] 337012 0
COMPOSITE SECONDARY OUTCOME= Maternal co-morbidities and risk factors for infection as assessed by maternal self-report and medical record review. For our study, a co-morbidity and risk factor for infection is anything other than a normal viable pregnancy from 20 weeks gestation until 6 months post-partum
Timepoint [4] 337012 0
up until 6 months post-partum
Secondary outcome [5] 337013 0
PRIMARY OUTCOME=Stillbirths as assessed by maternal self-report and medical record review
Timepoint [5] 337013 0
at birth
Secondary outcome [6] 337015 0
PRIMARY OUTCOME=Pregnancy complications as assessed by maternal self-report and medical record review. For our study a pregnancy complication is one that involves anything other than a normal viable pregnancy greater than 20 weeks gestation resulting in a live infant born at term.
Timepoint [6] 337015 0
up until 6 months post-partum
Secondary outcome [7] 337017 0
PRIMARY OUTCOME=infant morbidities as assessed by maternal self-report and medical record review. For our study, an infant morbidity will be defined as any illness requiring medical attention or review.
Timepoint [7] 337017 0
up until 6 months post-partum
Secondary outcome [8] 337268 0
PRIMARY OUTCOME=infant deaths as assessed by medical record review
Timepoint [8] 337268 0
up until 6 months post-partum
Secondary outcome [9] 337270 0
PRIMARY OUTCOME=All cause infant hospitalisations as assessed by maternal self-report and medical record review
Timepoint [9] 337270 0
up until 6 months post-partum
Secondary outcome [10] 337274 0
PRIMARY OUTCOME=Birth complications as assessed by maternal self-report and medical record review. For our study a birth complication is one resulting in anything other than a normal vaginal birth of a live infant.
Timepoint [10] 337274 0
Up until 6 months post-partum

Eligibility
Key inclusion criteria
i. Mothers – any pregnancy greater than or equal to 20 weeks gestation
ii. Infants born greater than or equal to 20 weeks gestation and/or weighing greater than or equal to 400grams
iii. Singleton infants from singleton pregnancies
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
i. Non-pregnant women
ii. Multiparous pregnancies (pregnancies where the woman is carrying more than one fetus)
iii. Infants who are a twin, triplet or other multiple birth
iv. Participants in the ‘FluMum’, ‘PneuMum’ and ‘1+1HS’ datasets where maternal vaccination status is unknown

Study design
Purpose
Duration
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Effect estimates from univariable and multivariable logistic regression models will be presented as adjusted odds-ratios, accounting for clustered data where applicable. Expected incidence rates (IR’s) of adverse maternal and infant perinatal outcomes will be calculated using an historic, largely unvaccinated 20-year population birth cohort (1994–2014), and compared with the observed incidence rates (IR’s) in maternally vaccinated (influenza, pertussis, pneumococcal) and unvaccinated pregnant mothers. Standardised incidence ratios (SIR) will be calculated using Poisson regression with 95% confidence intervals.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 296993 0
University
Name [1] 296993 0
Charles Darwin University
Address [1] 296993 0
Ellengowan Drive, Casuarina NT 0810
Country [1] 296993 0
Australia
Primary sponsor type
Other
Name
Menzies School of Health Research
Address
Level 1,147 Wharf Street
Spring Hill, Brisbane
QLD, 4000
Country
Australia
Secondary sponsor category [1] 296000 0
None
Name [1] 296000 0
Address [1] 296000 0
Country [1] 296000 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298191 0
Menzies School of Health Research Human Research Ethics Committee
Ethics committee address [1] 298191 0
Human Research Ethics Committee of the NT Department of Health and Menzies School of Health Research PO Box 41096, Casuarina NT 0811.
Ethics committee country [1] 298191 0
Australia
Date submitted for ethics approval [1] 298191 0
02/06/2016
Approval date [1] 298191 0
03/06/2016
Ethics approval number [1] 298191 0
HREC-2015-2333

Summary
Brief summary
Retrospective descriptive analysis of the safety of maternal vaccination utilising 4 datasets: ‘FluMum’, ‘PneuMum’, ‘1+1HS’ and a population based de-identified NT birth cohort. Combined datasets ~85,000 mother-infant pairs, of which ~30% identify as Aboriginal and/or Torres Strait Islander. There is no active participant recruitment, no blood tests or specimen collections and no direct contact with any participants. Results will be presented as large aggregate data with no potential for identifying information. Results will contribute novel information on adverse maternal and infant perinatal outcomes over a 21 year period (1994-2015) .We will calculate ‘Observed-to-Expected’ ratios to describe the risk of an adverse outcome occurring following maternal vaccination in pregnancy with influenza, pertussis or pneumococcal vaccines.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76278 0
Ms Lisa McHugh
Address 76278 0
Menzies School of Health Research, Charles Darwin University
Level 1,147 Wharf Street
Spring Hill, Brisbane
QLD, 4000
Country 76278 0
Australia
Phone 76278 0
+61 7 3169 4209
Fax 76278 0
Email 76278 0
lisa.mchugh@menzies.edu.au
Contact person for public queries
Name 76279 0
Ms Lisa McHugh
Address 76279 0
Menzies School of Health Research, Charles Darwin University
Level 1,147 Wharf Street
Spring Hill, Brisbane
QLD, 4000
Country 76279 0
Australia
Phone 76279 0
+61 7 3169 4209
Fax 76279 0
Email 76279 0
lisa.mchugh@menzies.edu.au
Contact person for scientific queries
Name 76280 0
Ms Lisa McHugh
Address 76280 0
Menzies School of Health Research, Charles Darwin University
Level 1,147 Wharf Street
Spring Hill, Brisbane
QLD, 4000
Country 76280 0
Australia
Phone 76280 0
+61 7 3169 4209
Fax 76280 0
Email 76280 0
lisa.mchugh@menzies.edu.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary