Child outcomes after prenatal progesterone for prevention of preterm birth, follow-up of the AMPHIA trial

Preterm birth is one of the major problems in obstetrics, complicating 5-13% of all pregnancies worldwide and is the most important cause of neonatal morbidity and mortality. Multiple pregnancy is a strong risk factor for preterm birth, with an incidence of delivery before 37 weeks of gestation of 53% in the Netherlands. Up to date there is convincing evidence for the use of progesterone in women with a singleton pregnancy and a history of preterm birth. In this group, the administration of progesterone shows a potential reduction of early preterm birth of 40%. Subsequently, progesterone is extensively studied as an intervention to prevent preterm birth in other high risk pregnancies (e.g. short mid-trimester cervix and multiple pregnancy). Use of progesterone is wide-spread, although little is known about the long-term effects of progesterone on the fetus and development and health of the child in later life.
The AMPHIA trial randomized women with a multiple pregnancy between 2006 and 2008 to weekly injections of either 250 mg 17α-hydroxyprogesterone caproate or placebo, starting between 16 and 20 weeks of gestation and continued until 36 weeks of gestation or delivery, whichever came first. This long-term follow-up will assess all children age 11-4 years born to mothers who participated in the AMPHIA trial using internationally validated questionnaires.

Due to its ability to avoid preterm birth, the neurodevelopmental sequelae of preterm birth could also be prevented by progesterone. However, progesterone may also exert direct effects on the fetus’ developing brain.

We will need a run-in period of 6 months for the study set up, and 24 months for inclusion. After inclusion of the last patient, 9 months will be needed for data collection and report of results. The first report on the results is expected at 3 years after the start of the study.

Progesterone