Combined tetanus, diphtheria, and pertussis (Tdap) vaccination during the second or third trimester of pregnancy does not appear to be associated with clinically significant harm to the fetus or neonate, according to findings from a systematic review of the literature.

However, the findings are limited by a dearth of randomized, placebo-controlled trials.

Across 21 mainly retrospective studies included in the review, point estimates ranged from 0.47 to 1.50 for preterm birth, 0.65 to 1.00 for small for gestational age, 0.36 to 0.85 for stillbirth, 0.16 to 1.00 for neonatal death, 0.76 to 1.20 for low birth weight, and 0.20 to 0.91 for congenital anomalies.

Point estimates for all anomalies after Tdap vaccination ranged from 1.20 to 1.60, Mark McMillan of the University of Adelaide, North Adelaide, Australia and his colleagues reported (Obstet Gynecol. 2017;129:560-73).

“Statistical imprecision for combined ‘all anomalies’ outcomes meant that upper 95% [confidence intervals] were 2.0 or above,” the researchers wrote. “Statistical imprecision was even greater in the individual congenital anomaly outcomes and little confidence can be placed in these estimates.”

Additionally, one of three studies assessing chorioamnionitis showed a small but significant increase in risk (relative risk, 1.19) after vaccination.

Among the studies examining medically attended adverse events, no association was seen between vaccination and such events or reactions, including neurologic events, gestational diabetes, preeclampsia or eclampsia, and cardiac events. Maternal effects included fever in 1%-3% of subjects, and headache, malaise, and myalgia, which were more common.

“Overall, despite the limitations described, the review offers reassurance for antenatal Tdap or Tdap-IPV [diphtheria, tetanus, pertussis, and polio] vaccination administered during the second or third trimester of pregnancy,” the researchers wrote. “These findings need to be interpreted in the context of the evidence of effectiveness of antenatal vaccination programs at preventing serious morbidity and mortality from pertussis in young infants.”

Mr. McMillan received travel support from GlaxoSmithKline, and institutional research grants from GSK and Sanofi Pasteur. Other researchers also reported receiving research funding and/or travel support from these companies.