Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial.

Authors:
Daan Barug
Daan Barug
Spaarne Hospital
Inge Pronk
Inge Pronk
National Institute for Public Health and the Environment
Netherlands
Mirjam J Knol
Mirjam J Knol
University Medical Center Utrecht
Netherlands

Lancet Infect Dis 2019 Apr 27;19(4):392-401. Epub 2019 Mar 27.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands. Electronic address:

Background: Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination offers protection for neonates against clinical pertussis until primary vaccinations, but maternal antibodies also interfere with infants' immune responses to primary vaccinations. We investigated the effect of maternal Tdap vaccination on the pertussis antibody responses of infants starting primary vaccinations at age 3 months.

Methods: In an open-label, parallel, randomised, controlled trial, pregnant women aged 18-40 years with a low risk of pregnancy complications were recruited through independent midwives at 36 midwife clinics in the Netherlands and received Tdap vaccination either at 30-32 weeks of pregnancy (maternal Tdap group) or within 48 h after delivery (control group). All term-born infants were vaccinated with the diphtheria, tetanus, and pertussis-inactivated poliomyelitis-Haemophilus influenzae type B-hepatitis B six-in-one vaccine and a ten-valent pneumococcal vaccine at 3 months, 5 months, and 11 months. Randomisation was done using a number generator in a 1:1 ratio and with sealed envelopes. Participants and clinical trial staff were not masked, but laboratory technicians were unaware of study group assignments. The primary endpoint was serum IgG pertussis toxin antibody concentrations at age 3 months. Cord blood and infant blood samples were collected at age 2 months, 3 months, 6 months, 11 months, and 12 months. Analysis was done by modified intention to treat with all randomly assigned participants in case a laboratory result was available. This trial is registered with ClinicaltTrialsRegister.eu (EudraCT 2012-004006-9) and trialregister.nl (NTR number NTR4314). The trial is now closed to new participants.

Findings: Between Jan 16, 2014, and March 4, 2016, 118 pregnant women were enrolled into our study, with 58 in the maternal Tdap group and 60 in the control group. The geometric mean concentration (GMC) of pertussis toxin antibodies were higher in infants in the maternal Tdap group than in the control group infants at age 3 months (GMC ratio 16·6, 95% CI 10·9-25·2) and also significantly higher compared with control infants at age 2 months. After primary vaccinations, antibody concentrations for pertussis toxin, filamentous haemagglutinin, and pertactin were significantly lower at all timepoints in infants of the maternal Tdap group than in infants in the control group. No safety issues after maternal Tdap vaccination were encountered.

Interpretation: In view of the high pertussis toxin antibody concentrations at age 3 months, maternal vaccination supports a delay of the first pertussis vaccination in infants until at least age 3 months. Maternal antibody interference affects antibody concentrations after primary and booster vaccinations. The clinical consequences of this interference remain to be established.

Funding: The Dutch Ministry of Health, Welfare, and Sport.

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(18)30717-5DOI Listing
April 2019
3 Reads

Publication Analysis

Top Keywords

months months
24
age months
24
maternal tdap
24
tdap group
16
primary vaccinations
16
pertussis toxin
16
antibody concentrations
16
control group
16
tdap vaccination
16
months
14
infants age
12
maternal
11
infants
9
group
9
pertussis vaccination
8
randomised controlled
8
infants maternal
8
controlled trial
8
tdap
8
group infants
8

Altmetric Statistics

Similar Publications