Maternal Antibody in Milk After Vaccination (MAMA)

Single-centre observational pilot study exploring pertussis specific antibody concentration in the breastmilk of women vaccinated against pertussis in pregnancy at different gestational ages. This study is made up of two stages: first stage to confirm recruitment methods and optimise the laboratory assay and a second stage to complete recruitment for the pilot study.

Study Overview

• Status: Unknown
• Conditions: Pertussis; Pregnancy; Vaccination; Breastmilk
• Intervention / Treatment: Biological: Boostrix-IPV

Detailed Description

Pertussis disease is a highly infectious respiratory illness caused by Bordetella pertussis, which can cause significant morbidity and mortality. There has been an increase in cases in many high income countries with high vaccination coverage and in an attempt to control this, antenatal vaccination programmes have been introduced in several countries, including the UK. Vaccination in pregnancy is a strategy which seeks to boost the maternal antibody levels, increase the placental transfer of antibody and consequently increase the antibody levels in the infant.

Human breast milk is a dynamic source of nutrition for the infant and is made up of many immunologically active components including antibody. The principal antibody in breastmilk is IgA and it has been shown that the amount of disease specific antibody in breastmilk can be increased by vaccination in pregnancy for a number of pathogens including pertussis. Secretory IgA (sIgA) plays an important role in immune exclusion in which it blocks adhesion of a pathogen onto a mucosal surface. As the first step of pertussis pathogenesis is the adhesion of bacteria to the ciliated respiratory epithelium in the nasopharynx and trachea there is a clear biological rationale for the hypothesis that receiving breast milk containing more IgA could enhance neonatal immunity and consequently the protective effects of vaccination in pregnancy.

The best time in pregnancy for administering the pertussis vaccination is debated in the literature, with some advocating vaccination in the second trimester and others supporting later vaccination to coincide the time of serum antibody peak with optimum placental transfer. This issue has been considered exclusively from the perspective of serum immunoglobulin G (IgG), but the impact of timing of vaccination in pregnancy on IgA levels in milk may also be important. Previous studies have shown that there is a peak in the pertussis specific IgA in breast milk at day 10 following vaccination, which then declines, and consequently there may be a significant difference in the amount of IgA available in the breastmilk for an infant born to a mother vaccinated at 20 weeks for example, compared to a mother vaccinated at 32 weeks. This may therefore have an impact on future guidelines on optimal time of vaccination in pregnancy.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• United Kingdom
  • London
    • Tooting, London, United Kingdom, SW17 0QT
      • Recruiting
      • St Georges University Hospital NHS Foundation Trust
      • Contact: Anna Calvert; Email: acalvert@sgul.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women who received a pertussis vaccination between 16 and 32 weeks and are pregnant or within 48 hours of delivery.

Description

Inclusion Criteria:

• Singleton pregnancy
• Received pertussis vaccination between 16 and 32 gestational weeks
• Planning to breastfeed

Exclusion Criteria:

• Received vaccination outside of the 16-32 week window
• Not planning to breastfeed
• Diagnosis of an immunodeficiency syndrome
• Multiple pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women vaccinated at less than 24 weeks; Women receiving a pertussis containing vaccine at less than 24 weeks	Biological: Boostrix-IPV; Receipt of Boostrix IPV at three different gestational time periods
Women vaccinated at 24-27+6 weeks; Women receiving a pertussis containing vaccine at 24-27+6 weeks	Biological: Boostrix-IPV; Receipt of Boostrix IPV at three different gestational time periods
Women vaccinated at 28-31+6 weeks; Women receiving a pertussis containing vaccine at 28-31+6 weeks	Biological: Boostrix-IPV; Receipt of Boostrix IPV at three different gestational time periods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti PT IgA at less than 48 hours in colostrum	Anti-pertussis toxin (PT) Immunoglobulin A (IgA) concentration in colostrum	Within 48 hours of delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total IgA and IgG in colostrum and breastmilk	Total IgA and IgG concentration in colostrum and breastmilk	Within 48 hours and at 14 and 42 days after delivery
Anti-PT IgA concentration in breastmilk	Anti-PT IgA concentration in breastmilk	At 14 and 42 days following delivery
Anti-PT IgG concentration in colostrum and breastmilk	Anti-PT IgG concentration in colostrum and breastmilk	Within 48 hours and at 14 and 42 days after delivery
Anti PT IgG concentration in maternal serum	Anti PT IgG concentration in maternal serum	Within 48 hours of delivery

Collaborators and Investigators

• Sponsor: St George's, University of London
• Collaborators: European Society for Paediatric Infectious Diseases
• Investigators: Study Director: Kirsty Le Doare, St George's, Univeristy of London

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 7, 2018
• Primary Completion (ANTICIPATED): August 31, 2019
• Study Completion (ANTICIPATED): October 31, 2019

Study Registration Dates

• First Submitted: June 10, 2019
• First Submitted That Met QC Criteria: June 10, 2019
• First Posted (ACTUAL): June 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2019
• Last Update Submitted That Met QC Criteria: June 10, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Whooping Cough
• Other Study ID Numbers: 18.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No