Maternal Tdap Vaccination and Neonatal Immunity, Timing Key

Jennifer Garcia

October 09, 2018

Maternal immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine early in the third trimester results in higher pertussis antibody concentrations in neonates compared with earlier or later immunization during pregnancy, according to a study published in the October 9 issue of JAMA.

"Pertussis toxin antibody concentrations at birth were sufficiently high in infants born to Tdap-immunized mothers that, even allowing for the natural decay of maternal antibodies, most infants would have had substantial antibody levels until initiation of the primary vaccine series, thus reducing their risk of pertussis-related mortality and morbidity," write lead author C. Mary Healy, MD, from the Baylor College of Medicine, Houston, Texas, and colleagues.

Previous studies of pertussis immunity in infants, including a recent report examining a 2016 pertussis outbreak in California, have demonstrated that timing of maternal immunization is integral to decreasing the risk for pertussis infection in neonates.

The Advisory Committee on Immunization Practices recommends vaccinating pregnant women with Tdap as early as possible between 27 and 36 weeks' gestation during every pregnancy to prevent neonatal infection, but the optimal timing in that window has been unclear.

In the current prospective observational study, Healy and colleagues evaluated data from 626 mother–infant pairs at a tertiary referral center between December 2013 and March 2014. Infants were eligible if there was clear record of their mother being vaccinated during pregnancy or not being vaccinated.

Among these, 312 women received a Tdap vaccine between weeks 27 through 36 (mean 31.2 weeks) and 314 were not vaccinated.

The authors found that the geometric mean concentration (GMC) of pertussis toxin antibodies in cord blood in the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1 - 53.2) compared with 12.9 IU/mL (95% CI, 11.7 - 14.3) in the Tdap-unexposed group, resulting in a ratio of 3.6 (95% CI, 3.1 - 4.2; P < .001).

The ratio remained significant even after controlling for factors such as maternal age, ethnicity, and gestational age at delivery.

Further, the neonatal pertussis antibody increased sequentially each week when Tdap vaccine was administered during 27 through 29 weeks of gestation, reached its peak when administered at week 30 (GMC 57.3 IU/mL; 95% CI, 44.0 - 74.6), and declined thereafter.

Although the optimal antibody level required to confer protective immunity in infants is not clear, the researchers found that Tdap-exposed infants had antibody levels well above those considered to be protective until the standard infant immunization series began.

The authors acknowledge study limitations such as the fact that all data were collected from a single center and the observational nature of the study does not allow for a cause-and-effect interpretation of the findings.

"This study demonstrated that, following US immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels," conclude Healy and colleagues.

Funding for this study was provided by the Centers for Disease Control and Prevention. Healy has received research grants from Sanofi Pasteur and Novartis Vaccines and has served on advisory boards for Novartis Vaccines, Pfizer, and Novavax. Another author has served on the scientific advisory board for Seqirus and as a consultant for Pfizer. The other authors have disclosed no relevant financial relationships.

JAMA. 2018;320:1464-1470. Abstract

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