Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial.
BACKGROUND
15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies.


METHODS
We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16-20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length.


CONCLUSIONS
This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies.


BACKGROUND
Current Controlled Trials ISRCTN40512715.
Lim
Arianne C
AC
Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands. A.C.Lim@amc.nl
Bloemenkamp
Kitty W M
KW
Boer
Kees
K
Duvekot
Johannes J
JJ
Erwich
Jan Jaap H M
JJ
Hasaart
Tom H M
TH
Hummel
Pieter
P
Mol
Ben W J
BW
Offermans
Jos P M
JP
van Oirschot
Charlotte M
CM
Santema
Job G
JG
Scheepers
Hubertina C J
HC
Schöls
Willem A
WA
Vandenbussche
Frank P H A
FP
Wouters
Maurice G A J
MG
Bruinse
Hein W
HW
D000077713:17 alpha-Hydroxyprogesterone Caproate; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000008:administration & dosage*; D007231:Infant, Newborn; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D011256:Pregnancy Outcome; D018566:Pregnancy, High-Risk; D011272:Pregnancy, Multiple; D011372:Progestins / Q000008:administration & dosage*; D016896:Treatment Outcome
D006908:Hydroxyprogesterones; D011372:Progestins; D000077713:17 alpha-Hydroxyprogesterone Caproate