A New Vision for Preterm Birth Prevention? the Use of Progesterone Therapy

Preterm birth is defined as delivery that occurs before 37 completed weeks from the first day

of the last menstrual period.  The U.S. preterm birth rate is now 12.7%, which is an increase of

more than 20% since 1990.  Improvements in the care and treatment of premature infants has

improved the survivor rates, but recent data continues to show that preterm birth has

had a significant impact on infant mortality.  In addition, preterm birth prevention rates have

gone unchanged.     The current methods for the diagnosis and treatment of preterm birth are based on inadequate

literature.   Interventions are based on the medical model of identifying each suspected

cause or risk factor for preterm birth with the expectation that the preterm birth rate

would decrease.  Despite these randomized controlled trials, the overall rate of preterm birth

continues to steadily rise. 

      Physiology of pregnancy is an important aspect of understanding preterm birth.  The woman,

fetus, and placenta act as one functional unit to sustain pregnancy until delivery.  Contributing to

this functional unit are several hormones types which include estrogen, androgens, and

progestogens.  Progesterone and 17 alpha-hydroxyprogesterone (17-OHP) are the major

progestogens in pregnancy.  These naturally occurring hormones have many actions and play an

important role in maintaining pregnancy. When 17-OHP is exposed to caproic acid, 17 alpha-

hydroxyprogesterone caproate (17-P) is created.  In this form, 17-P has been shown to have

twice the progestational activity and acts twice as long when compared to free progesterone.   Of all the treatments researched for preterm birth prevention, progestational agents such as

progesterone supplementation, have demonstrated the greatest promise.  In 2003, the publication

of two large randomized placebo controlled trials of 17-P and progesterone suppositories

rekindled interest in the obstetric arena.  Unlike studies that targeted multiple risk factors, these

studies evaluated supplemental progesterone as an effective method of reducing the rates of

preterm birth in women who had a history of a prior preterm delivery.    The primary clinical trial was sponsored by the NICHD and conducted by the Maternal-Fetal

Medicine Units Network. This   clinical trial was terminated early because efficacy was attained at

the time of the interim analysis.  Final results showed a 34% reduction in preterm births prior to 37+0 weeks.           Currently, 17-P is not commercially available in the United States and is compounded by

pharmacists.  Injections should ideally be started between 16+0 weeks and 20+6 weeks gestation. 

Injections should be concluded at 36+6 weeks or at the time of birth.  The most common side

effects reported by women were injection site pain and swelling.   A new drug application has

been submitted to the FDA.  If approved, the proposed dosing regimen would be called Gestiva.          Preterm birth and it’s consequences are considered one of the nation’s highest health care

priorities.  Focusing on prevention through the use of progesterone may lead to a significant

reduction in preterm birth. Nursing has a responsibility to understand the physiology of

progesterone in pregnancy as well as the implications that make 17-P a powerful tool in preterm

birth prevention.