Pre-Eclampsia, Diphtheria, Tetanus and Pertussis Vaccine Reaction
Conditions
Keywords
Preeclampsia, Tdap vaccinations
Brief summary
Preeclampsia is a significant medical condition occurring in 3-8% of pregnancies and impacts deleteriously both maternal and fetal health. An important discovery has been made by Dr Craig D Scoville showing that early Tdap vaccinations in pregnancy can reduce the incidence of preeclampsia by more than 50%. A prospective clinical research trial is proposed and urgently needed to validate this finding and thereby make a significant contribution in reducing the incidence of this common and severe complication of pregnancy.
Detailed description
A double blinded randomized prospective clinical research study is proposed to validate the hypothesis that Tdap vaccinations at week 28 in pregnancy can reduce the incidence of preeclampsia by more than 50%. This project will recruit 1600 pregnant women with appropriate informed consent in the first trimester of pregnancy, obtain detailed obstetric and health history, and then randomize these subjects so 800 women receive Tdap at week 28, and 800 women receive Tdap at week 36, and all women will be followed during their pregnancies using standard of care with special attention to preeclampsia and fetal outcomes. Blood samples will be obtained at weeks 12, 20, and 36 in order to test the anti-tetanus toxoid antibody levels, anti-diptheria antibody levels, anti-pertussis antibody levels, and also maternal cytokines (IL-2, IL-4, IL-6, IL-10, TNFa, IL-17, and IFNg), and placental biomarkers (sFlt-1, sEng, and PIGF) for preeclampsia on those patients who develop preeclampsia and compare to those who didn't and thereby better understand the biomarkers of preeclampsia and devise a better formula for positive prediction for preeclampsia. To make this change in clinical practice and save lives, this study is asking for funding from NICHD PA-18-480.
Interventions
Tdap vaccinations are routinely given during pregnancy between weeks 27 and 36 per guidelines of American College Obstetrics and Gynecology (ACOG) -- but this study uniquely is trying to establish that the earlier Tdap vaccinations reduce preeclampsia by more than 50%
Sponsors
Louisiana State University Health Sciences Center in New Orleans
Brigham Young University
Institute of Arthritis Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Each study site will designate an injection nurse who will be responsible for preparing both placebo and Tdap administration and will be the only one knowing when a patient gets either Tdap injection at week 28 or placebo injection at week 28, or gets Tdap injection at week 36 or placebo injection at week 36. This person will be the only one at each site who will know the randomization of each subject and is the only one who will administer the injection. Every subject will receive Tdap either at week 28 or week 36 and receive placebo injection on the other injection time.
Intervention model description
Pregnant women enlisted in the double blinded study will be randomized to receive Tdap vaccination either at week 28 or week 36 and observed and treated with standard of care.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
Yes
Inclusion criteria
1. confirmed pregnancy at week 12 2. Age 18 to 42 3. Willing to participate and sign informed consent documentation 4. willing to follow study procedures with regards to randomization of Tdap and attend all routine clinic visits per obstetrician and standard of care 5. accept Tdap vaccination either at week 28 or week 36
Exclusion criteria
1. no history of allergic reaction or intolerance to Tdap vaccination 2. No history of cancer in past 5 years prior to this study (except for non melanoma localized skin cancers or cancer in situ) -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of preeclampsia in each arm of the study with regards to timing of Tdap vaccination | Through duration of pregnancy approximately 10 months | The definition of preeclampsia in this study will follow the guidelines of ACOG inclusive of hypertension, proteinuria, but also other features |
| Incidence of preeclampsia in each arm of the study with regards to the quantitative anti-tetanus toxoid antibody level | Through duration of pregnancy approximately 10 months | Test the hypothesis that pregnant women with anti-tetanus toxoid antibody levels \<1.0 IU/ml are at higher risk of preeclampsia compared to those with higher levels. Obtain blood levels for anti-tetanus toxoid antibody levels, anti-pertussis antibody levels, and anti-diptheria antibody levels will be tested at weeks 12, 20, and 36 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of other potential risk factors for preeclampsia inclusive of BMI, hypertension, prior history of preeclampsia, first pregnancy | Through duration of pregnancy approximately 10 months | Statistical analysis of all possible variables for preeclampsia |
Other
| Measure | Time frame | Description |
|---|---|---|
| Compare the placental and maternal biomarkers of preeclampsia in order to devise a better formula for positive prediction of preeclampsia | Through duration of pregnancy at 12, 20 and 36 week of gestation | Follow the quantitative levels of maternal cytokines in pg/ml: IL-2, IL-4, IL-6, IL-10, TNFa, IL-17, IFNg and placental biomarkers in pg/ml PIGF during pregnancy at weeks 12, 20, and 36 and compare these levels with those women who develop preeclampsia to normal pregnancy cohorts from this study during the same times tested |
Countries
United States
Contacts
Primary ContactCraig D Scoville, MD,PhD
Backup ContactMaritza Rosales
Outcome results
None listed