There was no association between pregnant mothers who received the influenza or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines and the risk of infant death or hospitalization, researchers found.
In the case-control study, there was no such increased risk in the first 6 months of life among infants whose mothers received these vaccines, reported Lakshmi Sukumaran, MD, of the CDC, and colleagues.
Writing in Pediatrics, they noted that the Advisory Committee on Immunization Practices (ACIP) currently recommends both the Tdap and influenza vaccines during pregnancy — with a preference for the Tdap vaccine to be administered from 27 to 36 weeks gestation, specifically to protect infants from pertussis disease.
Maternal immunization with these vaccines allows for “passive antibody transfer” to infants to protect them before they are eligible to receive the vaccine, the authors argued, citing the high hospitalization and mortality rates linked with pertussis cases in infants younger than 6 months, and the high hospitalization rate from influenza for young infants. The researchers also noted that 18 of 96 influenza-associated pediatric deaths occurred in children younger than 6 months during the 2013-2014 flu season.
But, Sukumaran et al added, despite “reassuring safety data,” vaccine safety is the primary reason cited by providers and patients who choose not to vaccinate during pregnancy, and that there are “limited safety studies” beyond the immediate neonatal period.
“Although the biologic plausibility is unclear for the association of maternal vaccination and infant hospitalization or death, there may be concerns of long-term effects on infants after any pregnancy exposure,” the researchers wrote.
They examined singleton live birth pregnancies in the Vaccine Safety Datalink from 2004 to 2014. Vaccine exposure was defined as a vaccine given from 7 days after the pregnancy to 7 days before the pregnancy end date. Infant controls were required to have at least one diphtheria-tetanus-acellular pertussis (DTaP) vaccine between 6 weeks and 6 months, to ensure that infants were “accessing the healthcare system.”
Overall, 413,034 live births were included. Among them, there were 25,222 infants with one or more hospitalizations and 157 deaths in the first 6 months of life. Of the hospitalized infants, about 18% had a respiratory cause for hospitalizations; about 2% had an influenza ICD-9 code and 3% had a pertussis ICD-9 code.
Examining infant deaths, the researchers found that 9% had a respiratory cause of death, though none were “considered caused by” influenza or pertussis infections. The most common causes of death were unknown causes (32%), sudden infant death syndrome (21%), and “certain conditions originating in the perinatal period” (17%). The mean age at death was 61 days, with a range of 1 to 180 days.
Hospitalized infants were more likely to have had mothers with pregnancy complications, but less likely to have been delivered via cesarean delivery or be of African American non-Hispanic or American Indian race, the authors added.
There was no association between infant hospitalization and maternal influenza vaccination (adjusted OR 1.00, 95% CI 0.96-1.04) or Tdap vaccination (adjusted OR 0.94, 95% CI 0.88-1.01), and none between infant mortality and maternal influenza vaccine (adjusted OR 0.96, 95% CI 0.54-1.69) or Tdap vaccine (adjusted OR 0.44, 95% CI 0.17-1.13).
However, the authors noted a “protective effect” associated with maternal Tdap vaccination and infant respiratory hospitalizations (adjusted OR 0.79, 95% CI 0.67-0.94, P=0.007). The researchers noted that this is consistent with the results of other published studies that looked at infant pertussis, but pointed out that only 3% of infants “hospitalized for respiratory causes” had a pertussis ICD-9 code. This could mean either that “infants with pertussis are not being appropriately diagnosed and tested” or there are other contributing factors, the team speculated.
Limitations to the data, the researchers said, include that the Vaccine Safety Datalink captures data on an insured population, and has a high rate of women with “adequate prenatal care” (which often translates into better health outcomes), and that there is a potential for bias because controls were required to have a DTaP vaccine record for inclusion to ensure access to healthcare utilization.
The study was supported by the Centers for Disease Control and Prevention (CDC); the Vaccine Safety Datalink project is funded by the CDC.
Sukumaran and co-authors reported having no conflicts of interest, and noted that the findings and conclusions are those of the authors and do not necessarily represent the official position of the CDC.