Clinical trial NCT01322516: Outcomes of Pandemic Influenza in Pregnancy
Official title: Outcomes of Pandemic Influenza in Pregnancy: an Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Influenza
Lead sponsor: Dalhousie University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2011-03-24
Enrollment: 200
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 800 pregnant women followed through pregnancy during second and third waves of the 2009 influenza pandemic, and 2009/10 influenza season. Forty percent are high risk pregnancies: either for maternal influenza complications (eg. underlying asthma, gestational diabetes mellitus in prior pregnancies) or high risk for obstetrical complications (eg. prior premature birth, multiple pregnancies). Recruitment from Halifax, Quebec City, Toronto, Hamilton, Calgary, Edmonton, and Vancouver. Plan to enroll all women before the beginning of the second wave; however, enrolment of women \<20 weeks pregnant will continue at each site until the second wave has peaked locally.

Brief summary: We propose to follow a cohort of pregnant and post-partum Canadian women through the fall and winter of 2009/2010 and the anticipated second and third waves of the current pandemic in order to better understand the incidence, complications and risk factors for severe disease due to H1N1 influenza in pregnant women, and to contribute data on the safety and effectiveness of antivirals and vaccines in this population.

The primary hypotheses to be tested are:

(i) pandemic influenza infection in the second and third trimester of pregnancy is associated with an increase in adverse fetal outcomes (fetal loss, stillbirth, neonatal mortality, significant neonatal morbidity, prematurity) (ii) close contact with young children (\<2 yrs) at home or work is the most important risk factor for influenza in pregnant women (iii) higher scores on a scale of community infection prevention (a combination of self-reported hand hygiene adherence, avoidance of ill persons and avoidance of crowds) are protective against influenza (iv) receipt of seasonal influenza vaccine from 2007 to 2009 will increase the risk of illness due to influenza A(H1N1)v in the second and third waves of the pandemic.

(v) pandemic influenza vaccine is effective in preventing symptomatic influenza in pregnant women.

(vi) vaccination of pregnant women against a particular strain of influenza protects their infants against influenza infection in the first six months of life.

Detailed description: Subjects will be consented to participate in the study. They will complete a web-based baseline questionnaire. Participants will be given a nasal swab kit with instructions for obtaining swabs. Baseline blood (10mls) will be drawn for influenza serology and for measurement of total IgG and IgG subtypes. An email will be sent to each participant within 24 hours of their enrolment to welcome them to the study.

Participants will be asked to complete a weekly diary using web-based data entry. An email will be sent to each participant every Monday during the study reminding the participant to complete their weekly diary and to report and submit a nasal swab if they have any symptoms of an acute respiratory illness. Reminder emails will be sent 48 hours later if the weekly form remains incomplete. Participants will be telephoned if forms remain incomplete for three weeks. Weekly emails will also be used to update participants about vaccine availability, current vaccine recommendations, and any changes in expert recommendations for pregnant women.

Once every four weeks additional questions will be asked on the weekly survey. If any participant develops symptoms compatible with an acute viral respiratory illness they will be asked to collect and submit a nasal swab as soon as possible after the onset of symptoms and to complete an illness starting the day of symptom onset and ending when all symptoms are either absent or mild, or for 3 days, whichever is longer. Subjects will be notified if results are positive for influenza along with the local Medical Officer of Health. Treatment for influenza will be discussed with each infected participant by a physician investigator.

Repeat serology and blood for total IgG and IgG subtype will be drawn at the time of delivery to the six week post partum. Women will notify the study when they are admitted for delivery or termination of pregnancy and will be interviewed either in person at the hospital, or over the telephone within 3 weeks of delivery. A chart review will be performed to identify any complications at delivery or termination, and to record neonatal outcomes. Post-partum, mothers will continue their own weekly and illness diaries and weekly diaries for their infants will be added.

Pregnant women requiring hospital admission for influenza in hospitals participating in surveillance for the Toronto Invasive Bacterial Diseases Network (TIBDN) and Serious Outcomes Surveillance (SOS) for the PHAC/CIHR Influenza Research Network (PCIRN), as well as pregnant women with influenza admitted to intensive care units as part of the Canadian Critical Care Clinical Trials Group Influenza Surveillance System (ICU-Flu) will be approached. Risk factor data from the baseline and weekly questionnaires will be collected retrospectively from these women. With consent, women will be followed to delivery/termination, and the same information collected regarding neonatal outcomes as was collected for other women in the cohort.

An email will be sent to all participating women requesting their consideration of three additional parts of the study:

1. A questionnaire of development (the 8 month Ages and Stages® Questionnaire; see attached) to be completed by the parent
2. An assessment with a physical examination at 7-9 months of age by a trained physician or a nurse practitioner
3. Permission for the study to contact parents in the future about further follow-up.

Mothers will also be asked to book an appointment for the 7-9 month assessment. Mothers who do not wish to have a pediatrician assessment will be asked over the telephone if they have any questions they wish to have answered about the study or the Ages and Stages® questionnaire, and if they consent to contact for future long term follow-up studies. If the child's score on the Ages and Stages® questionnaire raises a concern, mothers will be offered the chance to discuss this with a study physician, to have the results shared with her child's physician and/or to be referred to a pediatrician.

Participants may choose to withdraw from the study at any time. When they do so, they will be asked if the data and blood samples that have been provided can be kept and used for study purposes. If a patient withdraws and cannot be contacted data that has been obtained will be retained, and blood will be used for the immediate study purpose, but will not be used for future studies.

Eligibility criteria: Inclusion Criteria:

* Participants must:

  1. be and pregnant, and, at the time of enrolment, not more than 30 weeks gestation.
  2. be greater than or equal to 16 years of age
  3. give written informed consent prior to entry
  4. be available for follow-up during the study period
  5. have convenient access to a computer with internet access
  6. know basic skills for use of the internet
  7. have the ability to complete questionnaires in either English or French

Exclusion Criteria:

* None

Primary outcomes:
measure: Influenza A(H1N1)v infection: will be as diagnosed by polymerase chain reaction(PCR) from nasal or nasopharyngeal (NP) swabs, and/or seroconversion to influenza A(H1H1)v.
timeFrame: October 2009 to June 2010
Secondary outcomes:
measure: Adverse fetal/neonatal outcome.
timeFrame: October 2009-June 2010
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Edmonton
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia's Women's and Children's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Ottawa
country: Canada
facility: Public Health Agency of Canada
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: Laval University
state: Quebec
Study officials:
affiliation: Dalhousie University, Halifax, NS
name: Shelly McNeil, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Laval University, Montreal, Quebec
name: Emmanuel Bujold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto, Toronto, Ontario
name: Allison McGeer, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University, Hamiton, Ontario
name: Mark Loeb, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary, Calgary, Alberta
name: Marie Louie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta, Edmonton, Alberta
name: George Zahariadis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia, Vancouver, British Columbia
name: Deborah Money, MDFRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: Public Health Agency of Canada, Ottawa, Ontario
name: Rachel Rodin, MD
role: PRINCIPAL_INVESTIGATOR
References: