Tdap Vaccine More Effective in Second Trimester of Pregnancy

The majority of preterm neonates benefited from a maternal tetanus-diphtheria-acellular pertussis (Tdap) immunization performed during the second rather than the third trimester of pregnancy, according to a brief report published in Clinical Infectious Diseases.

Christiane Eberhardt, MD, from the department of neonatology and pediatric intensive care at the Children’s Hospital of Geneva in Switzerland, and colleagues conducted a single-center prospective observational study in pregnant women delivering before gestation week (GW) 37 0/7 to find the optimal timing for Tdap maternal vaccination.

The study, conducted at the University Hospitals of Geneva, Switzerland between August 2014 and February 2016, measured anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibodies by enzyme-linked immunosorbent assay. Cord blood samples of preterm neonates were collected to measure anti-PT and anti-FHA antibodies after maternal Tdap immunization was given in the second trimester (GW 13 0/7 and 25 6/7) or third trimester (after GW 25 6/7) of pregnancy.

Of the 85 women who were Tdap-immunized, 37 were immunized during the second trimester and 48 during the third trimester. A total of 17 preterm neonates were born between GW 30 0/7 and 33 6/7 and 68 were born between GW 34 0/7 and 36 6/7.

Birth antibody geometric mean concentrations (GMCs) were significantly higher in the second semester compared with the third semester for anti-PT (41.3 EU/mL [95% CI 29.6 to 57.5] vs 22.1 EU/mL [95% CI 14.3 to 34.2]; P =.024) and for anti-FHA antibodies (201.1 EU/mL [95% CI 149.7 to 270.1] vs 120.2 EU/mL [95% CI 80.6 to 179.2]; P =.040).

In the multivariable analysis, after adjustment for maternal age, gestational age at birth, parity, and socioeconomic status, the ratio of second to third trimester anti-PT antibodies remained statistically significant (2.04 [95% CI 1.15 to 3.61]; P =.016).

The study also found that none of the 37 preterm neonates born after second trimester maternal immunization were seronegative vs 11 of the 48 preterm neonates in the third-trimester group. Seronegativity was defined as anti-PT ≤5 EU/mL.

Researchers noted that an interval of 15 days was sufficient enough to observe higher cord antibody titers and that the number of seronegative neonates grew as gestational age increased.

“The transplacental transfer of maternal antibodies is effective sufficiently early in gestation so that the majority of preterm neonates born between GW 30 0/7 and 36 6/7 benefit from a maternal Tdap immunization performed during the second trimester of pregnancy,” the researchers concluded.

Because this was an observational study, confounding factors influencing antibody transfer could not be ruled out. Moreover, the study did not include data for preterm neonates born before GW 30 0/7 and thus “lacked [the] power to detect an effect for preterm births between GW 30 0/7 and 33 6/7.” Further studies are needed to determine the benefits of early maternal immunization for very early preterm neonates.

Reference

Eberhardt CS, Blanchard-Rohner G, Lemaître B, et al. Pertussis antibody transfer to preterm neonates after second- versus third-trimester maternal immunization [published online March 14, 2017]. Clin Infect Dis. doi: 10.1093/cid/cix046