Pertussis Immunization During Pregnancy: Effect in Term and Preterm Infants (MAMA)

January 12, 2021 updated by: Elke Leuridan, MD, PhD, Universiteit Antwerpen

Pertussis Immunization During Pregnancy: Assessment of the Role of Maternal Antibodies on Immune Responses in Term and Preterm Infants: the MAMA Study

Young infants are most vulnerable to severe disease and even death when infected with Bordetella Pertussis. The current vaccines and vaccination programs do not guarantee protection of neonates. During the last weeks of pregnancy, maternal IgG antibodies are transferred actively to the fetus. Administration of a pertussis containing vaccine during pregnancy offers protection through high titers of maternal antibodies transferred to the child. Since transplacental transport is immature, infants who are born prior to 37 weeks of gestation, might be vulnerable to pertussis infection even though maternal vaccination was administered, but specific data are lacking. The primary aim of this observational study is to measure whether vaccination during pregnancy offers protection to preterm born infants through higher titers of maternal antibodies, despite immature transplacental transport. Four cohorts of mother-infant pairs will be recruited: term versus preterm born infants, born from either vaccinated women or not vaccinated women. These mother-infant pairs are recruited according to the vaccination status of the mother and to the gestational age at delivery. Pertussis specific antibody titers (anti-Pertussis Toxin, anti-Filamentous haemagglutinin, anti-Pertactin titers) will be monitored in blood samples of the mothers at delivery to measure the possible influence of both gestational age and maternal vaccination status. In order to measure the decline of maternal antibodies in the first weeks of life, blood will be taken from cords as well as from infants at 8 weeks of age, before the first infant pertussis vaccine is administered.

Pertussis antibodies to the same antigens will be measured in all infants after a primary series of acellular pertussis vaccines administered at 8,12 and 16 weeks of age and before and after a booster dose in the second year of life.

In addition, cellular mediated immune responses will be evaluated in a subgroup of infants before and after a primary series of infants vaccines. A last goal is to measure whether vaccination during pregnancy could offer additional maternal antibodies through breast milk. Again a comparison is made between preterm and term born infants, born from either vaccinated or unvaccinated women. The amount of lactoferrin and pertussis toxin specific IgA in breast milk samples will be measured in samples taken at birth (colostrum), and at several time points afterwards as long as breastfeeding is continued.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

232

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerp, Belgium, 2000
        • University of Antwerp

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Four cohorts of women-infant pairs will be recruited before or directly after delivery.

A cohort of preterm born infants will be compared to term born infants, and both will be compared within groups of vaccinated women (adult acellular pertussis containing vaccine) or unvaccinated women.

Description

Inclusion Criteria for participating women:

  • Pregnancy
  • Signed informed consent
  • Intend to be available for follow-up visits and phone call access through 16 months following delivery
  • Willing to have infant immunized with hexavalent vaccine according to the recommended Belgian schedule

Exclusion Criteria for participating women:

  • Significant mental illness (e.g. schizophrenia, psychosis, major depression)
  • Serious underlying immunological condition (e.g. immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection)
  • Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk
  • Receipt of a blood product or experimental medicine within 4 weeks prior to delivery
  • Multiple pregnancies

Exclusion Criteria for children:

  • No signed informed consent from both parents
  • Severe reactions to any vaccine
  • Serious underlying medical condition (e.g., genetic disorder (eg Down syndrome), immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection, lung/heart disease, liver/kidney disease, chronic or recurrent infections)
  • Children suffering from primary humoral immune disorders (B cell related): severe X linked agammaglobulinaemia, CVID (Common variable immunodeficiency, late onset agammaglobulnaemia) and SAD (specific antibody deficiency); suffering from primary cellular immune deficiencies (T cell related): SCID (Severe combined immune deficiency syndrome), CID, hyper IGM syndrome, di George's syndrome and others; suffering from disorders in phagocytosis and chemotaxis (CGD, Schwach Diamond syndrome) and disorders from the complement cascade
  • In addition children with oncologic disorders will be excluded. All these children can receive the inactivated pertussis vaccines, but will respond different from the normal population to vaccination.
  • Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Preterm born infants of vaccinated women
Preterm born infants (< 37 weeks of gestation) whose mothers have received an acellular pertussis vaccine during pregnancy, within the national recommended vaccination programme. Infant vaccination against pertussis is performed according to the national recommended schedule.
Drug: Infant pertussis vaccination
Infants receive pertussis vaccines according to the national recommended schedule
Other Names:
  • Infant pertussis containing vaccination
Term born infants vaccinated women
Term born infants (>= 37 weeks of gestation) whose mothers have received an acellular pertussis vaccine during pregnancy, within the national recommended vaccination programme. Infant vaccination against pertussis is performed according to the national recommended schedule.
Drug: Infant pertussis vaccination
Infants receive pertussis vaccines according to the national recommended schedule
Other Names:
  • Infant pertussis containing vaccination
Term born infants unvaccinated women
Term born infants (>= 37 weeks of gestation) whose mothers have not received an acellular pertussis vaccine during pregnancy. Infant vaccination against pertussis is performed according to the national recommended schedule.
Drug: Infant pertussis vaccination
Infants receive pertussis vaccines according to the national recommended schedule
Other Names:
  • Infant pertussis containing vaccination
Preterm born infants unvaccinated women
Preterm born infants (< 37 weeks of gestation) whose mothers have not received an acellular pertussis vaccine during pregnancy.Infant vaccination against pertussis is performed according to the national recommended schedule.
Drug: Infant pertussis vaccination
Infants receive pertussis vaccines according to the national recommended schedule
Other Names:
  • Infant pertussis containing vaccination

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Titers of maternal pertussis specific antibodies
Time Frame: From birth until 8 weeks of age
Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken from cord and at week 8 postpartum in all participating infants
From birth until 8 weeks of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Titers of pertussis specific antibodies in infants after 3 doses of a pertussis vaccine
Time Frame: At the age of 5 months
Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken at 5 months (after a primary series of 3 vaccines)
At the age of 5 months
Titers of pertussis specific antibodies in infants before and after a fourth dose of a pertussis vaccine
Time Frame: From 13 to 16 months
Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken before and 1 month after a fourth pertussis vaccine
From 13 to 16 months
Titers of pertussis specific antibodies in infants in-between the fourth and fifth dose of a pertussis vaccine
Time Frame: Around 3 years of age
Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken before and 1 month after a fourth pertussis vaccine
Around 3 years of age
Titers of pertussis specific antibodies in infants before and after a fifth dose of a pertussis vaccine
Time Frame: From 5 to 6 years of age
Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken before and 1 month after a fourth pertussis vaccine
From 5 to 6 years of age
Th1 immune responses in preterm and term born infants before and after a primary series of infant pertussis vaccines
Time Frame: From 8 weeks of age until 16 months of age
Measurement of Th1 markers in a convenience sample of infants after primary and booster pertussis vaccination
From 8 weeks of age until 16 months of age
Th2 immune responses in preterm and term born infants before and after a primary series of infant pertussis vaccines
Time Frame: From 8 weeks of age until 16 months of age
Measurement of Th2 markers in a convenience sample of infants after primary and booster pertussis vaccination
From 8 weeks of age until 16 months of age
Th1 & Th2 immune responses in preterm and term born infants before and after a fifth booster dose of a pertussis vaccine
Time Frame: From 5 to 6 years of age
Measurement of Th1 and Th2 markers in a convenience sample of infants before and after a pertussis booster vaccination
From 5 to 6 years of age
Titers of pertussis specific IgA antibodies in breast milk
Time Frame: From birth until 3 months postpartum
Measurement of anti-Pertussis Toxin IgA, total IgA and lactoferrin titers in breast milk samples taken at birth, at week 4, 8 and 12
From birth until 3 months postpartum

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universiteit Antwerpen

Collaborators

University Hospital, Antwerp
Research Foundation Flanders
Université Libre de Bruxelles

Investigators

  • Principal Investigator: Elke Leuridan, MD, PhD, Universiteit Antwerpen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Actual)

January 1, 2019

Study Registration Dates

First Submitted

July 22, 2015

First Submitted That Met QC Criteria

July 29, 2015

First Posted (Estimate)

July 30, 2015

Study Record Updates

Last Update Posted (Actual)

January 15, 2021

Last Update Submitted That Met QC Criteria

January 12, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • cev003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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