1. Prevention of Recurring Premature Birth Presentation for Health Care Providers June 2008

2. The Problem: Premature Birth 1:7 infants in NC is born preterm 1:5 African American infants is born preterm Increased 27% since 1982 and continues to grow Causes over 70% of perinatal morbidity and mortality

3. Recurring Premature Birth The most significant known risk factor is a history of preterm birth. Women with previous PTB are 21% to 45.1% more likely to have a preterm infant than other women.

4. What is 17P? 17P (17 alpha-hydroxyprogesterone caproate) is a synthetic form of progesterone given by injection in the gluteus muscle or anterior thigh Shown to reduce the risk of preterm birth among women with a history of a prior preterm birth

5. Effectiveness of 17P Reduces a woman’s risk of recurrent preterm birth by 33% The American College of Obstetricians and Gynecologists recommends the use of progesterone for secondary prevention of preterm birth

6. 17P is not a silver bullet for preterm birth prevention. However, it is an important option for a group of high- risk women and should be considered as part of every prenatal care provider’s list of intervention options.

7. Meta-analysis of 17P in Pregnancy 15 published trials of various progesterone compounds in women at high risk Pooled analysis of the results of the trials showed no effect on the rates of miscarriages or stillbirths 5 trials which treated high risk women with 17P Pooled analysis of the results showed: - Reduction in rates of preterm birth Odds ratio was.50, 95% CI: 0.30-0.85 - Reduction in rates of low birth weight Odds ratio was 0.46, 95% CI: 0.27-0.80 Meis, PJ., Wake Forest University, School of Medicine, May 2008, Progesterone for the Prevention of Preterm Birth Presentation

8. Study Results Published in New England Journal of Medicine 17P treatment was effective in both African American and Non-African American women 17P treatment was effective in preventing very early as well as later preterm births 17P Treatment of the women resulted in significant reductions in the rates of IVH and NEC for their infants Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003; 348:2379-85

9. 17P Actions on the Myometrium Decreases conduction of contractions Increases threshold for stimulation Decreases number of oxytocin receptors Suppresses the inflammatory cascade Inhibits T lymphocyte development Promotes expression of prostaglandin EP2 receptor Prevents formation of gap junctions Meis, PJ. May 2008, Progesterone for the Prevention of Preterm Birth Presentation

10. Safety of 17P Studies show no serious side effects for mother or baby No increase in the rate of birth defects for infants whose mothers use 17P No observed increase in health problems in children whose mothers used 17P

11. FDA Status 17P was originally FDA approved for use during pregnancy, though not for this indication.The sole remaining manufacturer ceased production of 17P in 1998, which automatically removed FDA approval. A company has applied to the FDA to approve the drug with the indication of preventing preterm delivery. The FDA ruled that the drug was "approvable" but additional tests were required. The results of those tests were favorable and approval is anticipated. This could increase the cost of 17P.

12. Protocol for 17P Use History of a previous singleton spontaneous preterm birth (20 0 to 36 6 weeks) Current singleton pregnancy Initiate treatment between 16 0 - 21 6 weeks gestation* Receive 17P injections weekly until 36 6 weeks gestation or she delivers Women who delivered multiple infants preterm and/or who are pregnant with multiples are not eligible for treatment

13. How to Administer 17P 1.Clean the vial top with an alcohol swab before use 2.Clean the injection site with an alcohol swab before administration 3.Draw up 1 ml of drug in a 3cc syringe with an 18- gauge needle 4.Change the needle to a 21-gauge 1.5 inch needle 5.Inject in upper out quadrant of the gluteus maximus. Rotate between left and right sides each week. 6.Store 17P at 20-25 degrees C (68-77 degrees F) in a dry place away from direct heat and sunlight

14. Ordering One simple way to order 17P is to use the www.mombaby.org website. Click on the 17P button. Use either the Medicaid or Uninsured portals. The drug will be sent to you in about 4 business days. www.mombaby.org You can use the pharmacies listed on the website to place an order for 17P for your privately insured patients. You can also use those pharmacies for Medicaid orders but be sure they conform w/ Medicaid policies. You will need a password from the project coordinator Be sure to include email addresses for the prescribing provider AND the provider entering the request.

15. Billing Providers who order 17P for Medicaid patients will receive a pharmacy bill of $90/10 dose vial or $60/5 dose vial. The provider then bills Medicaid $20/dose plus the injection fee. Uninsured patients can receive 17P free thanks to support from the General Assembly Providers should submit the 17P invoice directly to private insurers such as Tricare, Blue Cross Blue Shield of NC and the State Health Plan

16. Adding 17P to your Practice 1. Educate staff about treatment and protocol 2.Review billing procedures and confirm w/ administration 3. Review patient history for eligibility for 17P treatment 4.Counsel patient about the benefits / limitations of 17P, timeline for injections, and the importance of compliance 5. If the patient has Medicaid, inform her about the Maternity Care Coordination services. Find the nearby MCC services by calling 1-800-367-2229. 6. Work with the patient to help facilitate her receiving weekly injections.

17. Information for Patients Colorful, easy-to-read booklets in English and Spanish A short DVD in English and Spanish filmed by mothers for mothers Fact sheets (online) Some mothers may want to review the scientific articles on the mombaby website or view a longer video about 17P also on the site.

18. Other Considerations 17P does not guarantee a full term pregnancy 17P is dispensed in a multi-dose vial. This is helpful if a clinic has purchased a vial and then the mother delivers early or changes her mind. Patients should be counseled at every visit about maintaining health behaviors and recognizing the signs of preterm labor The benefits of partial therapy out weigh the risk of no therapy

19. Don’t Forget – Primary Prevention Strategies Promote lifestyle modifications - Good Nutrition - Cessation of use of Tobacco, Alcohol and Drugs - Increase Rest – Lower Stress Manage chronic conditions like diabetes or hypertension Screen for sexually transmitted infections Encourage routine dental exams Combat the effects of poverty, racism, and domestic violence Meis, PJ., Wake Forest University, May 2008, Progesterone for the Prevention of Preterm Birth Presentation.

20. Questions? Password? Contact Sarah Verbiest, MSW, MPH 919-843-7865 sarahv@med.unc.edu www.mombaby.org Thank you to Dr. Paul Meis for allowing citation of several of his slides.