Your Pregnancy Matters

Progesterone and premature birth: What a new study means for pregnant women

Your Pregnancy Matters

In 2003, the FDA approved injections of the hormone progesterone to help prohibit preterm births. But a 2019 trial indicates it may not be as effective as first thought.

Preterm birth, or being born before 37 weeks of pregnancy, is a significant problem in Texas, and the U.S. as a whole. In 2019, 10.6% of babies born in Texas were premature, slightly higher than the rate of 9.9% nationwide.

Prematurity was related to 34% of infant deaths in 2017. Babies who survive are at increased risk for a variety of issues, such as breathing problems, feeding difficulties, cerebral palsy, developmental delays, and vision and hearing problems.

Unfortunately, the causes of spontaneous preterm birth remain elusive. We know that once a woman has one premature delivery from spontaneous labor or rupture of membranes (when a woman’s “water breaks”), the risk of having another is two to three times higher. And the earlier the first preterm birth, the higher the possibility of preterm birth in the next pregnancy.

What can prevent preterm birth?

We know the pregnancy hormone progesterone helps prevent the uterus from contracting too soon, and there has been long-term interest in the possible use of it to prevent spontaneous preterm birth. 

In 2019, 10.6% of babies born in Texas were premature, slightly higher than the rate of 9.9% nationwide.

A large 2003 study in which we participated showed that weekly progesterone (17-OHPC) injections given to pregnant women with a history of at least one prior preterm delivery reduced the risk of delivery before 37 weeks by 34%. The infants born to that group of women also had fewer complications in the newborn period.

Based on the results of that study, the FDA conditionally approved a drug called Makena for the prevention of recurrent preterm birth. As a part of this process, a confirmatory study had to be performed.

However, results of that study, published in October 2019, showed no benefit to these weekly injections and an FDA advisory committee has voted to recommend the FDA withdraw its approval for Makena. 

Let’s discuss what we learned from the 2019 study, and what women with a history of preterm birth should do if they are pregnant or are considering pregnancy. 

What the new study reveals about preventing premature birth

In the most recent study, called the PROLONG trial, the rate of preterm birth was similar in women who received progesterone and those who received placebo injections. Neonatal deaths and complications also did not differ dramatically among the groups.

What might explain the difference between the two studies? Re-examination of the first study showed the process of randomization was less than ideal. Studies that compare two therapies require that the patients in the two treatment groups are similar. In the earlier study, the women who received the placebo had more risk factors for preterm birth than the women who were given progesterone injections.

The rate of premature birth in women who received a placebo was more than 50% – higher than expected and planned for in the trial. On the other hand, women who received progesterone had a preterm birth rate of 36%, making the treatment look as if it was effective at reducing preterm births. 

The 2019 study, however, found the risk of having a premature birth was about 22% to 23% in both groups. 

What to do if you’ve had a premature birth

What does this mean for women who have had a spontaneous preterm birth due to early labor or rupture of membranes in the past?

First, it’s important to note that we’re talking about a very specific treatment for recurrent preterm birth. It doesn’t impact therapies such as vaginal progesterone given to women at risk of premature delivery due to a short cervix.

While the FDA advisory committee recommended withdrawing approval of Makena, it’s unlikely to happen soon. Professional societies like the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine are not walking away from current recommendations that support its use.

According to ACOG, “Consideration for offering 17-OHPC to women at risk for recurrent preterm birth should continue to take into account the body of evidence for progesterone supplementation, the values and preferences of the pregnant woman, the resources available, and the setting in which the intervention will be implemented.” 

If you’ve had a premature baby in the past, going into another pregnancy may cause you to feel stressed or anxious. It’s important to remember that what happened was not your fault – and just because it happened in one pregnancy doesn’t mean it’s certain to happen again.

Related readingApproaching pregnancy after a difficult experience

Talk to your provider about your history and whether they think progesterone therapy is right for you. If you would like to talk to a doctor about a current or planned pregnancy, call 214-645-8300 or request an appointment online.