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

Sponsor

Universiteit Antwerpen (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02511327

Collaborator

University Hospital, Antwerp (Other), Université Libre de Bruxelles (Other), Research Foundation Flanders (Other)

232

Enrollment

Location

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pertussis	Drug: Infant pertussis vaccination

Study Design

Study Type:

Observational

Actual Enrollment :

232 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Jan 1, 2019

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

Titers of maternal pertussis specific antibodies [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

Secondary Outcome Measures

Titers of pertussis specific antibodies in infants after 3 doses of a pertussis vaccine [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)
Titers of pertussis specific antibodies in infants before and after a fourth dose of a pertussis vaccine [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
Titers of pertussis specific antibodies in infants in-between the fourth and fifth dose of a pertussis vaccine [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
Titers of pertussis specific antibodies in infants before and after a fifth dose of a pertussis vaccine [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
Th1 immune responses in preterm and term born infants before and after a primary series of infant pertussis vaccines [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
Th2 immune responses in preterm and term born infants before and after a primary series of infant pertussis vaccines [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
Th1 & Th2 immune responses in preterm and term born infants before and after a fifth booster dose of a pertussis vaccine [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
Titers of pertussis specific IgA antibodies in breast milk [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.