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Observational Study
. 2016 Apr 1;62(7):829-836.
doi: 10.1093/cid/ciw027. Epub 2016 Jan 20.

Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant Seropositivity Against Pertussis

Christiane S Eberhardt  1   2 , Geraldine Blanchard-Rohner  3 , Barbara Lemaître  4 , Meriem Boukrid  5 , Christophe Combescure  6 , Véronique Othenin-Girard  5 , Antonina Chilin  5 , Jean Petre  7 , Begoña Martinez de Tejada  5 , Claire-Anne Siegrist  1   3
Affiliations
Observational Study

Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant Seropositivity Against Pertussis

Christiane S Eberhardt et al. Clin Infect Dis. .

Abstract

Background: Maternal immunization against pertussis is currently recommended after the 26th gestational week (GW). Data on the optimal timing of maternal immunization are inconsistent.

Methods: We conducted a prospective observational noninferiority study comparing the influence of second-trimester (GW 13-25) vs third-trimester (≥GW 26) tetanus-diphtheria-acellular pertussis (Tdap) immunization in pregnant women who delivered at term. Geometric mean concentrations (GMCs) of cord blood antibodies to recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) were assessed by enzyme-linked immunosorbent assay. The primary endpoint were GMCs and expected infant seropositivity rates, defined by birth anti-PT >30 enzyme-linked immunosorbent assay units (EU)/mL to confer seropositivity until 3 months of age.

Results: We included 335 women (mean age, 31.0 ± 5.1 years; mean gestational age, 39.3 ± 1.3 GW) previously immunized with Tdap in the second (n = 122) or third (n = 213) trimester. Anti-PT and anti-FHA GMCs were higher following second- vs third-trimester immunization (PT: 57.1 EU/mL [95% confidence interval {CI}, 47.8-68.2] vs 31.1 EU/mL [95% CI, 25.7-37.7], P < .001; FHA: 284.4 EU/mL [95% CI, 241.3-335.2] vs 140.2 EU/mL [95% CI, 115.3-170.3], P < .001). The adjusted GMC ratios after second- vs third-trimester immunization differed significantly (PT: 1.9 [95% CI, 1.4-2.5]; FHA: 2.2 [95% CI, 1.7-3.0], P < .001). Expected infant seropositivity rates reached 80% vs 55% following second- vs third-trimester immunization (adjusted odds ratio, 3.7 [95% CI, 2.1-6.5], P < .001).

Conclusions: Early second-trimester maternal Tdap immunization significantly increased neonatal antibodies. Recommending immunization from the second trimester onward would widen the immunization opportunity window and could improve seroprotection.

Keywords: maternal antibodies; maternal immunization; neonates; pertussis; pregnancy.

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Figures

Figure 1.
Figure 1.
Anti–pertussis toxin (PT) and anti–filamentous hemagglutinin (FHA) cord blood antibody concentrations by trimester of maternal immunization. Individual anti-PT and anti-FHA antibody concentrations in newborns of mothers vaccinated with tetanus-diphtheria-acellular pertussis during the second or the third trimester; each point corresponds to 1 patient. Geometric mean concentrations and 95% confidence intervals are indicated. The dotted line indicates the cutoff for expected infant seropositivity (anti-PT = 30 enzyme-linked immunosorbent assay units [EU]/mL).
Figure 2.
Figure 2.
Distribution of anti–pertussis toxin (PT) and anti–filamentous hemagglutinin (FHA) infant cord blood antibody concentrations according to time between maternal tetanus-diphtheria-acellular pertussis (Tdap) immunization and delivery. The curves represent the distribution of individual anti-PT (A) and anti-FHA (B) antibody concentration (log10) at various time intervals between maternal Tdap immunization and delivery. The vertical line indicates the cutoff for expected infant seropositivity (anti-PT ≥30 enzyme-linked immunosorbent assay units [EU]/mL).
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Comment in

  • Optimal Timing of Immunization Against Pertussis During Pregnancy.
    Abu Raya B, Srugo I, Bamberger E. Abu Raya B, et al. Clin Infect Dis. 2016 Jul 1;63(1):143-4. doi: 10.1093/cid/ciw233. Epub 2016 Apr 18. Clin Infect Dis. 2016. PMID: 27090990 No abstract available.
  • Reply to Abu Raya et al.
    Eberhardt CS, Martinez de Tejada B, Siegrist CA. Eberhardt CS, et al. Clin Infect Dis. 2016 Jul 1;63(1):144-5. doi: 10.1093/cid/ciw235. Epub 2016 Apr 18. Clin Infect Dis. 2016. PMID: 27090994 No abstract available.

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