Pessaries in mulitple pregnancy as a prevention of preterm birth

Preterm birth is the major cause of handicaps in genetically normal children
despite the enormous advanced neonatal care during the last decades. So,
prevention of preterm birth is the major goal of obstetrical care. However,
strategies to prevent preterm birth have been largely unsuccessful.

Twin pregnancies are at high risk for preterm birth. In the Netherlands about
15% of the women with a multiple pregnancy deliver before 34 weeks of
gestation. At present, about 1 in 60 pregnancies is a twin pregnancy, and about
30% of the preterm born children admitted in a neonatal care (NICU) are from
twin pregnancies (Source: LVR (Dutch Obstetrical Database), LNR (Dutch Neonatal
Database)). Due to an increase in age of pregnant women and an increase in
assisted reproductive technologies the incidence of twin pregnancies is still
rising.

The financial burden of preterm born babies is enormous: about ¤ 1500,- per day
when admitted in a NICU with the concomitant costs in case the child appears to
be handicapped, for both parents as the society in general. The composite poor
neonatal outcome contains severe RDS, broncho pulmonal dysplasia (BPD),
intraventricular haemorrhage II B or worse (IVH), periventricular leucomalacia
(PVL), necrotizing entercolitis (NEC), sepsis and death before discharge
(Guinn). The prevalence of this composite neonatal outcome is 77%, 35% and 12%
in children born after early preterm delivery between 24-27, 28-32 and 32-34
weeks, respectively. After 34 weeks this incidence sharply declines to less
than 2% at term. The probability that a woman delivers at these gestational
ages is 1.8%, 5.4% and 7.2%, respectively. In total, this means that about 8%
of the multiple pregnancies will result in the death of at least one child,
whereas in 7% of the pregnancies at least one of the children will remain
severely disabled. Moreover, another 20% of the pregnancies results in a
moderate handicap of at least one of the children.

Women with a twin pregnancy are seen by a gynaecologist for their antenatal
care. Although preterm birth is known to be the most important complication of
a twin pregnancy no general accepted strategy is available to prevent this
condition.

Recently, it has been shown that prophylactic progesterone administration to
women with a singleton pregnancy at high risk for a preterm birth significantly
reduced the incidence of preterm birth. Since then, several trials have been
set up to assess whether progesterone is effective in the prevention of preterm
birth in women with a multiple pregnancy. The first trial that was published on
this subject disappointingly showed no effect of progesterone in the prevention
of preterm birth in these women.

At present, this issue is also investigated in our nationwide consortium for
obstetric trials. Our trial has at present recruited 560 of the needed 660
women, and is supposed to be completed in July 2009. Several other trials will
be completed also.

Although a no data are known at present, we anticipate a negative treatment
effect.

In this proposal, we aim to evaluate an intervention with a cervical pessary
that will be inserted any time between 12 and 20 weeks and continued till
delivery or 36 weeks gestation, whatever comes first.

With this design the hypothesis whether the use of a cervical pessary can
reduce the preterm birth rate in twin pregnancies and its concomitant composite
neonatal morbidity can be answered.

To investigate the hypothesis that in women with a multiple pregnancy
prophylactic use of a pessary will be effective in the prevention of preterm
delivery and the neonatal mortality and morbidity resulting from preterm
delivery.

To assess in women with a multiple pregnancy the cost-effectiveness of a
pessary in the prevention of preterm delivery and the neonatal mortality and
morbidity resulting from preterm delivery.

Multicenter randomised study. The study will not be blinded. The study will be
stratified for parity (previous vaginal delivery or not), chorionicity
(multichorial versus monochorial) and number of multiples (twin or higher order
gestation).

Eligible women will be randomly allocated to receive either a cervical pessary
or no intervention. The cervical pessary will be placed in situ at 16 to 20
weeks, and will stay in situ up to 36 weeks gestation.

De burden and risks for women participating in this study will be minimal. When
a patient is randomly selected to use a pessary, it wil be placed between 16
and 20 weeks gestation. The number of visits to the outpatient clinic will not
differ much from the number of normal visits during a multiple pregnancy. The
women will undergo an ulstrasound measurement of the cervix, which in some
participating centres is standard protocol for women with a multiple pregnancy.

Next to this research intervention cases are treated according to the local
protocol in the participating clinics and other interventions i.e. tocolysis
and corticosteroids in case of a threatened preterm birth.