Welcome to the Medicines in Pregnancy Journal Club
Join us for our second #MedsPregJC (and first of 2020) on Wednesday 26th February 2020. This time we will be discussing the recently published article by Hall et al. on the safety of tetanus, diphtheria and acellular pertussis (Tdap) vaccine among pregnant women. During the Twitter JC we will critically appraise the study and discuss implications for practice and future research.
Date: Feb 26th 2020 @ 9pm GMT.
Article citation: Hall C, Abramovitz LM, Bukowinski AT, Ricker AA, Khodr ZG, Gumbs GR, et al. Safety of tetanus, diphtheria, and acellular pertussis vaccination among pregnant active duty US military women. Vaccine. 2020. https://www.sciencedirect.com/science/article/pii/S0264410X2030013X
TwitterJC host: Prof. Brian Cleary, Rotunda Hospital, Dublin, Ireland.
How to get involved: (1) Follow @MedsPregnancyJC (2) Search the hashtag #MedsPregJC to follow the discussions (3) Contribute to @MedsPregnancyJC by including #MedsPregJC in your tweets.
A summary of the study ‘Safety of tetanus, diphtheria, and acellular pertussis vaccination among pregnant active duty US military women‘ is provided below. Join us on 26th Feb 2020 @9pm GMT for further discussion.
Aim: Assess the safety of inadvertent (0–13 weeks’ gestation) and recommended (27–36 weeks’ gestation) exposure to the Tdap vaccine in pregnancy.
Study design: Retrospective cohort study.
Data source: U.S. Department of Defense Birth and Infant Health Research (BIHR) data, encompassing demographic and U.S. military personnel data linked with administrative medical claims from domestic and overseas duty locations.
Inclusion criteria: Pregnancies from 2006 to 2014 among U.S. military women who were on active duty status for the duration of their pregnancy
Exclusion criteria: Pregnancies for which outcomes could not be ascertained (pregnancies that could not be defined as live deliveries or losses due to loss to follow-up (including those with a lapse in military health system enrolment, or discontinuation of pregnancy care) or conflicting pregnancy data, ectopic and molar pregnancies, pregnancies ending in elective abortions, pregnancies in which women received more than one Tdap vaccine and multiple gestations.
Exposure: Record of Tdap vaccine administration in military personnel immunization data. Exposure was categorised as inadvertent exposure (receipt of Tdap vaccine between 0 and 13 weeks’ gestation) or recommended exposure (receipt of Tdap vaccine between 27 and 36 weeks’ gestation).
- Adverse pregnancy outcomes: Pre-eclampsia, preterm labour, and spontaneous abortion (>22 weeks’ gestation), identified using ICD and CPT codes.
- Adverse infant outcomes: Low birth weight (<2500g), preterm birth (<37 weeks’ gestation), growth problems in utero, growth problems in utero, and major birth defects.
Confounders: Maternal age at conception (Continuous), Marital status (Married or unmarried/unknown), Military rank (Enlisted or officer), Military service rank (Army, Navy, Air force, Marine Corps or Coast Guard), Receipt of vaccines not routinely recommended in pregnancy (Yes or no, used as a proxy for lack of pregnancy recognition), Infant birth year.
Analysis: Multivariable Cox and generalized linear regression models were used to estimate Hazard Ratios (HR) and Risk Ratios (RR) between Tdap vaccine exposure and adverse pregnancy or infant outcomes.
- 145,883 pregnancies to active duty women between 2006-2014 were included.
- 1272 women were exposed to the Tdap vaccine in the first trimester and 9438 women were exposed between 27 and 36 weeks’ gestation.
- 984 infants were exposed to the Tdap vaccine in the first trimester and 9352 exposed to Tdap vaccine between weeks 27-36 weeks’ gestation.
- Receipt of Tdap vaccine in the first trimester or between 27-36 weeks’ gestation was not associated with preeclampsia (First trimester: aHR 1.02 [95%CI: 0.78-1.34]; 27-36weeks’ gestation: aHR 1.07 [95%CI: 0.97-1.17]), preterm labour (First trimester: aHR 0.94 [95%CI: 0.74-1.19]; 27-36weeks’ gestation: aHR 0.97 [95%CI: 0.88-1.07]), or spontaneous abortion (First trimester: aHR 1.07 [95%CI: 0.94-1.22]).
- Receipt of Tdap vaccine in the first trimester or between 27-36 weeks’ gestation was not associated with adverse infant outcomes, including: birth defects (First trimester: aRR 15 [95%CI: 0.82-1.61]), growth problems in utero (First trimester: aRR 0.85 [95%CI: 0.58-1.25]; 27-36weeks’ gestation: aRR 1.03 [95%CI: 0.91-1.16]), growth problems in infancy (First trimester: aRR 0.85 [95%CI: 0.61-1.20]; 27-36 weeks’ gestation: aRR 0.95 [95%CI: 0.85-1.06]), preterm birth (First trimester: aRR 0.77 [95%CI: 0.60-0.99]; 27-36weeks’ gestation: aRR 0.95 [95%CI:0.87-1.04]), or low birth weight (First trimester: aRR 0.71 [95%CI: 0.51-0.99]; 27-36weeks’ gestation: aRR 0.69 [95%CI: 0.61-0.77]).
- A higher proportion of infants whose mothers received the Tdap vaccine in the first trimester were male (54.8%), compared with infants whose mothers did not receive the Tdap vaccine in pregnancy (51.3%), aRR 1.07 [95%CI: 1.01-1.13].
- Possible exposure and outcome status misclassification.
- Potential inaccuracy in LMP (and therefore estimated gestational age) for pregnancy losses.
- Absence of information on other potential confounders such as smoking status and alcohol status.
- Potential for healthy user bias.
- Growth problems in-utero and major birth defects were only assessed among live born infants.
Author’s conclusions: No increased risks for adverse maternal, fetal, or infant outcomes was associated with Tdap vaccine during pregnancy.
Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.