Reviews
Progesterone for the Prevention of Preterm
Birth
A Systematic Review
Jodie M. Dodd, PhD, FRANZCOG, Vicki J. Flenady,
and Caroline A. Crowther, MD, FRANZCOG
OBJECTIVE: We performed a systematic review to assess
the benefits and harms of progesterone administration
for the prevention of preterm birth in women and their
infants.
DATA SOURCES: The Cochrane Controlled Trials Register was searched, and reference lists of retrieved studies
were searched by hand. No date or language restrictions
were placed.
METHODS OF STUDY SELECTION: Randomized trials
comparing antenatal progesterone for women at risk of
preterm birth were considered. Studies were evaluated
for inclusion and methodological quality. Primary outcomes were perinatal death, preterm birth before 34
weeks, and neurodevelopmental handicap.
TABULATION, INTEGRATION AND RESULTS: Eleven
randomized controlled trials (2,425 women and 3,187
infants) were included. For women with a history of
spontaneous preterm birth, progesterone was associated
with a significant reduction in preterm birth before 34
weeks (one study, 142 women, RR 0.15, 95% CI 0.04 –
0.64, number needed to treat 7, 95% CI 4 –17), but no
statistically significant differences were identified for the
outcome of perinatal death. For women with a short
cervix identified on ultrasound, progesterone was not
associated with a significant difference in perinatal death
From the Discipline of Obstetrics and Gynaecology, the University of Adelaide,
Adelaide, South Australia, Australia; the Centre for Clinical Research, the
Mater Mother’s Hospital, Brisbane, Australia; and the Mater Mother’s Hospital,
Brisbane, Australia.
Supported by the Australian National Health and Medical Research Council
Neil Hamilton Fairley Overseas Clinical Fellowship (ID 399224) to Dr. Dodd.
Corresponding author: Dr. Jodie Dodd, the University of Adelaide, Discipline of
Obstetrics & Gynaecology, Women’s and Children’s Hospital, 72 King William
Road, North Adelaide, South Australia 5006, Australia; e-mail: jodie.dodd@
adelaide.edu.au.
Financial Disclosure
The authors have no potential conflicts of interest to disclose.
© 2008 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/08
VOL. 112, NO. 1, JULY 2008
RN, MPH,
Robert Cincotta,
FRANZCOG,
(one study, 274 participants, RR 0.38, 95% CI 0.10 –1.40),
but there was a significant reduction in preterm birth
before 34 weeks (one study, 250 women, RR 0.58, 95% CI
0.38 – 0.87, number needed to treat 7, 95% CI 4 –25). For
women with a multiple pregnancy, progesterone was
associated with no significant difference in perinatal
death (one study, 154 participants, RR 1.95, 95% CI
0.37–10.33). For women presenting after threatened preterm labor, no primary outcomes were reported. For
women with “other” risk factors for preterm birth, progesterone was not associated with a significant difference
in perinatal death (two studies, 264 participants, RR 1.10,
95% CI 0.23–5.29).
CONCLUSION: Progesterone is associated with some
beneficial effects in pregnancy outcome for some women
at increased risk of preterm birth.
(Obstet Gynecol 2008;112:127–34)
P
reterm birth, defined by the World Health Organization as birth before 37 completed weeks of
gestation,1 is estimated to affect approximately 13
million births annually worldwide.2 The incidence of
preterm birth is reported to be between 5% and 11%,3,4
ranging from 4.4% in Ireland,5 7.6% in Canada,6 8.2% in
Australia,7 and 12.7% in the United States.8 The
prevention of preterm birth remains elusive, with
many reports indicating an increase in prevalence
during recent years.9 –11
Infants who are born preterm are more likely to
die during the neonatal period than are term infants,12,13 and although the risk is greatest for infants
born at earlier gestational ages, it remains evident for
infants born between 32 and 36 weeks of gestation.14
For surviving infants, the health implications of immaturity are significant, particularly in relation to
respiratory distress syndrome,15 and the subsequent
risk of developing chronic lung disease,16 and other
long-term handicaps including cerebral palsy.17
OBSTETRICS & GYNECOLOGY
127
The cause of preterm birth is multifactorial, with
the most significant and consistently identified risk
factor being a woman’s history of previous preterm
birth.18 –21 Other characteristics in a woman’s current
pregnancy placing her at increased risk of preterm
birth include the identification of short cervix by
ultrasound assessment and multiple pregnancy.
Progesterone has a role in maintaining pregnancy22–24 and is thought to act by suppressing smooth
muscle activity in the uterus.25,26 We performed a
systematic review to assess the benefits and harms of
progesterone administration for the prevention of
preterm birth in women and their infants.
SOURCES
We searched PubMed, the Cochrane Controlled Trials Register, and the International Clinical Trials
Register using the free text search terms pregnancy,
preterm birth, progesterone, progestogen, intramuscular, vaginal, oral, perinatal morbidity, perinatal
mortality, and randomis(z)ed controlled trial. The
reference lists of retrieved studies were searched by
hand, and no date or language restrictions were
placed (date of last search was January 2008).
STUDY SELECTION
All published randomized controlled trials in which
progesterone was administered for the prevention of
preterm birth were considered. Studies were subdivided by reason the women were considered to be at
risk for preterm birth, including past history of spontaneous preterm birth (including preterm premature
rupture of membranes), multiple pregnancy, ultrasound-identified short cervical length, and after presentation with symptoms or signs of threatened preterm labor. Trials were excluded if progesterone was
administered for the treatment of actual or threatened
preterm labor, if progesterone was administered for
preventing miscarriage, or if studies were available in
abstract form only.
The primary outcomes were perinatal mortality,
preterm birth before 34 weeks of gestation, and
developmental delay in childhood. The secondary
outcomes included threatened preterm labor, cesarean section, antenatal corticosteroids, use of antenatal
tocolysis, preterm birth at less than 37 weeks of
gestation, infant birth weight less than 2,500 g, respiratory distress syndrome, need for assisted ventilation, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, neonatal sepsis
(either culture-proven or presumptive), patent ductus
arteriosus, fetal death, and neonatal death.
128
Dodd et al
Progesterone for Preterm Birth
Studies under consideration were evaluated independently for appropriateness for inclusion and methodological quality without consideration of their results by all authors, according to the QUOROM
guidelines for systematic reviews of randomized trials.27 There was no blinding of authorship.
Assessment of quality considered generation of
the randomization sequence, allocation concealment,
blinding, and completeness of follow up. We defined
high-quality trials as those receiving an A rating for
blinding of randomization, blinding of the intervention, and less than 20% loss to follow-up for major
outcomes. For dichotomous data, relative risks (RRs)
and 95% confidence intervals (CIs) were calculated.
Primary analyses were based on intention to treat
principles. Planned subgroup analyses included an
assessment of the effect of 1) time of treatment
commencing (before 20 weeks of gestation versus
after 20 weeks of gestation), 2) route of administration
(intramuscular, intravaginal, oral, intravenous), and 3)
different dosage regimens (divided arbitrarily into a
cumulative dose of less than 500 mg per week and a
dose of greater than or equal to 500 mg per week).
Twenty-two studies were identified for consideration. Eleven studies met the inclusion criteria.28 –38
For use of progesterone in women with a history
of prior spontaneous preterm birth, four studies were
included, involving 1,307 women with a past history
of spontaneous preterm birth.30,34–36 Two of these compared weekly intramuscular injection with placebo,34,35
and two compared nightly vaginal progesterone with
placebo.30,36 The primary outcomes reported related
to preterm birth before 32 weeks of gestation36 and 37
weeks of gestation.30,34,35 The report by Northen39
details the 2-year follow-up of 278 participants from
the Meis randomized trial.35
Intramuscular Progesterone
The method of generating the randomization sequence was adequate in one study,35 with both studies
using identical-appearing treatment packs (allocation
concealment: A),34,35 and blinding of outcome assessment (blinding: A).34,35 There were no reported losses
to follow-up in the study by Meis35 and 14% postrandomization exclusions in the study by Johnson.34 Both
trials received a quality rating of A.
Vaginal Progesterone
The method of generating the randomization sequence was adequate in both studies,30,36 both using
sequentially numbered identical-appearing treatment
packs (allocation concealment: A) and blinded outcome assessors (blinding: A).30,36 Both studies re-
OBSTETRICS & GYNECOLOGY
ported less than 20% loss to follow-up (DaFonesca
10%, O’Brien 7.3%),30,36 and received a quality rating
of A.
For use of progesterone in women with a short
cervix identified on transvaginal ultrasound examination, a single study was included involving 250
women who were identified as having short cervix
(defined as less than 15 mm) at the time of transvaginal ultrasound examination.31 Women received either 200 mg nightly intravaginal progesterone or
placebo from 24 to 33 completed weeks of gestation.
The primary outcome related to the occurrence of
preterm birth before 34 weeks of gestation.
Vaginal Progesterone
The method of generating the randomization sequence was not stated.31 The study used central
randomization with identical-appearing treatment
packs (allocation concealment: A) and blinded outcome assessors (blinding: A).31 There were no reported losses to follow-up. The trial received a quality
rating of A.
For use of progesterone in women with a multiple
pregnancy, two studies were included, involving 738
women with a twin pregnancy28,32 who received
weekly intramuscular injections in a dose of 250 mg
or placebo. The primary outcomes reported included
a composite of death or birth before 35 weeks of
gestation.28
Intramuscular Progesterone
Hartikainen32 did not indicate the method of generation of the randomization sequence or allocation
concealment (allocation concealment: B) but indicated the use of blinded outcome assessors (blinding:
A) and reported no losses to follow-up, receiving an
overall quality rating of B. The trial by Rouse28
indicated the method of generation of the randomization sequence, used identical-appearing treatment
packs (allocation concealment: A), used blinded outcome assessors (blinding: A), reported 1% loss to
follow-up, and received an overall quality rating of A.
For use of progesterone in women after symptoms or signs of threatened preterm labor, two studies
involving 130 women presenting with symptoms or
signs of threatened preterm labor (including both
uterine contraction pattern and evidence of cervical
change) between 24 –25 and 34 weeks of gestation
were included, in which women were randomized
after the use of acute tocolysis to arrest uterine
activity.29,38 In the study by Borna,29 women received
either vaginal progesterone pessaries on a daily basis
(400 mg) from randomization until birth or no treat-
VOL. 112, NO. 1, JULY 2008
ment. The primary outcome reported was the interval
from randomization to birth. In the study by Fachinetti,38 women received either intramuscular progesterone (341 mg) every 4 days from randomization
until 36 weeks of gestation or no treatment. The
primary outcome reported was transvaginal ultrasound detection of short cervical length.
Intramuscular Progesterone
The study by Fachinetti38 used a random number
table to generate the randomization sequence, which
was managed by a senior midwife (allocation concealment: B). The study did not use blinded outcome
assessors (blinding: B), reported no losses to followup, and received a quality rating of B.
Vaginal Progesterone
The study by Borna29 used a random number table to
generate the randomization sequence. There was no
indication of the method of allocation concealment
(allocation concealment: B) and the study did not use
blinded outcome assessors (blinding: B) and reported
no losses to follow-up. The trial received a quality
rating of B.
For use of progesterone in women at risk of
preterm birth for “other” reasons, the study by Papiernik37 recruited 99 women with a “high preterm
risk score.” Women were allocated to receive either
intramuscular progesterone three times per week or
placebo.
The study by Hauth33 involved 168 women who
were considered to be at risk of preterm birth because
of active military service. Women received either
1,000 mg of intramuscular progesterone weekly or
placebo. The primary outcome for the study related
to the incidence of preterm birth at less than 37 weeks
of gestation.
Intramuscular Progesterone
Neither study33,37 indicated the method of randomization used or the process of allocation concealment
(allocation concealment: B), but both stated the use of
blinded outcome assessors (blinding: A) and reported
no losses to follow-up. Both trials received a quality
rating of B.
Three studies were excluded because they used a
quasi-randomized method of treatment allocation.40–42
One study43 compared an oral progestogen with
placebo but presented outcomes only as percentages.
Five studies were excluded because progesterone was
administered in the first trimester to prevent miscarriage.44 – 48 One study comparing progesterone with
cervical cerclage49 has been reported in abstract form
Dodd et al
Progesterone for Preterm Birth
129
only but was not included because insufficient information was presented.
RESULTS
Eleven randomized controlled trials involving a total
of 2,425 women and 3,187 infants were included in
the meta-analysis.
Progesterone Compared With Placebo for
Women With a Past History of Spontaneous
Preterm Birth
Primary Outcomes: For women administered progesterone during pregnancy, for the primary outcomes
perinatal death and developmental delay in childhood, there were no statistically significant differences
identified when compared with placebo. Women
administered progesterone were significantly less
likely to have a preterm birth at less than 34 weeks of
gestation (one study, 142 women, RR 0.15, 95% CI
0.04 – 0.64, number needed to treat to benefit 7, 95%
CI 4 –17). See Table 1.
Secondary Infant Outcomes: For women administered progesterone during pregnancy, when compared
with placebo, there was a statistically significant reduction in the risk of infant birth weight less than 2,500 g
(two studies, 501 infants, RR 0.64, 95% CI 0.49 – 0.83,
number needed to treat to benefit 7, 95% CI 5–17).
Secondary Maternal Outcomes: There were no statistically significant differences for the secondary maternal outcomes reported.
Route of Administration, Time of Commencing Therapy, and Dose of Progesterone: There was no differential
effect on the outcomes when considering route of
administration of progesterone, time of commencement of supplementation, or total weekly cumulative
dose of progesterone.
Progesterone Versus Placebo for Women With
a Short Cervix Identified on Ultrasound
Primary Outcomes: For women administered progesterone during pregnancy, for the primary outcome perinatal death, there were no statistically significant
differences identified when compared with placebo.
Women administered progesterone were significantly
less likely to have a preterm birth at less than 34
weeks of gestation (one study, 250 women, RR 0.58,
95% CI 0.38 – 0.87, number needed to treat to benefit
7, 95% CI 4 –25). See Table 2.
Secondary Infant Outcomes: For women administered
progesterone during pregnancy, when compared with
Table 1. Progesterone Versus Placebo in Women With a Prior Spontaneous Preterm Birth
Outcome
Primary
Perinatal death
Preterm birth at less than 34 wk
Developmental delay*
Secondary maternal
Threatened preterm labor†
Cesarean delivery
Antenatal corticosteroids
Antenatal tocolysis
Secondary infant
Preterm birth at less than 37 wk†
Birthweight less than 2,500 g
Respiratory distress syndrome
Need for assistedventilation
Intraventricular hemorrhage, all grades†
Intraventricular hemorrhage, grade 3 or 4
Retinopathy of prematurity
Necrotizing enterocolitis†
Neonatal sepsis
Patent ductus arteriosus
Fetal death
Neonatal death
No. Studies
Participants
Relative Risk
95% CI
3
1
1
1,114
142
275
0.65
0.15
0.97
0.38–1.11
0.04–0.64
0.55–1.73
2
2
2
3
601
1,070
1,070
1,114
0.87
1.01
0.92
1.11
0.47–1.62
0.82–1.23
0.73–1.16
0.81–1.52
4
2
2
1
2
1,255
501
1,069
459
1,070
0.68
0.64
0.79
0.59
0.54
0.45–1.02
0.49–0.83
0.57–1.10
0.35–1.01
0.12–2.47
2
1,069
1.59
0.21–11.75
1
2
1
1
3
3
458
1,070
459
459
1,114
1,114
0.50
0.25
1.13
0.44
0.85
0.56
0.15–1.69
0.03–2.46
0.35–3.59
0.16–1.18
0.35–2.03
0.28–1.10
CI, confidence interval.
Bold indicates statistically significant results.
* Developmental assessment using Ages and Stages Questionnaire.39
†
Significant statistical heterogeneity identified (I2 statistic in excess of 50%); random effects model used.
130
Dodd et al
Progesterone for Preterm Birth
OBSTETRICS & GYNECOLOGY
Table 2. Progesterone Versus Placebo in Women With a Short Cervix Identified on Ultrasound
Outcome
Primary
Perinatal death
Preterm birth at less than 34 wk
Secondary infant
Birth weight less than 2,500 g
Respiratory distress syndrome
Need for assisted ventilation
Intraventricular hemorrhage, all grades
Retinopathy of prematurity
Necrotizing enterocolitis
Neonatal sepsis
Fetal death
Neonatal Death
No. Studies
Participants
Relative Risk
95% CI
1
1
274
250
0.38
0.58
0.10–1.40
0.38–0.87
1
1
1
1
1
1
1
1
1
274
274
274
274
274
274
274
274
274
0.96
0.59
0.65
0.51
5.07
0.34
0.28
1.01
0.29
0.73–1.27
0.29–1.19
0.36–1.16
0.05–5.53
0.25–104.70
0.01–8.23
0.08–0.97
0.06–16.06
0.06–1.37
CI, confidence interval.
Bold indicates statistically significant results.
placebo, there was a statistically significant reduction in
the risk of neonatal sepsis (one study, 274 infants, RR
0.28, 95% CI 0.08 – 0.97, number needed to treat to
benefit 18, 95% CI 9 –163), but no other differences
were identified for other secondary infant outcomes.
Route of Administration, Time of Commencing Therapy, and Dose of Progesterone: It was not possible to
assess the effect of route of progesterone administration, gestational age at commencement of therapy, or
total cumulative dose of medication.
Progesterone Versus Placebo for Women With
a Multiple Pregnancy
Primary Outcomes: For women administered progesterone during pregnancy, for the primary outcomes
perinatal death and preterm birth at less than 34
weeks of gestation, there were no statistically signifi-
cant differences identified when compared with placebo. See Table 3.
Secondary Infant Outcomes: For women administered
progesterone during pregnancy, when compared with
placebo, there were no statistically significant differences
for the reported secondary infant outcomes.
Secondary Maternal Outcomes: For women administered progesterone during pregnancy, when compared with placebo, there was a statistically significant
reduction in the need for antenatal tocolysis (one
study, 654 women, RR 0.75, 95% CI 0.57– 0.97,
number needed to treat to benefit 14, 95% CI 8 –123).
Route of Administration, Time of Commencing Therapy, and Dose of Progesterone: There was no differential
effect observed when considering time of commencement of supplementation.
Table 3. Progesterone Versus Placebo in Women With a Multiple Pregnancy
Outcome
Primary
Perinatal death
Secondary maternal
Cesarean section
Antenatal corticosteroids
Antenatal tocolysis
Secondary infant
Preterm birth at less than 37 wk
Birth weight less than 2,500 g
Respiratory distress syndrome
Need for assisted ventilation
Intraventricular hemorrhage, grades 3 or 4
Retinopathy of prematurity
Necrotizing enterocolitis
Neonatal sepsis
Patent ductus arteriosus
No. Studies
Participants
Relative Risk
95% CI
1
154
1.95
0.37–10.33
1
1
1
652
654
654
0.99
0.91
0.75
0.88–1.12
0.70–1.17
0.57–0.97
2
1
1
1
1
1
1
1
1
732
1,276
1,280
1,280
1,280
1,280
1,280
1,280
1,280
1.01
0.94
1.13
0.93
1.20
NE*
0.77
0.95
0.60
0.92–1.12
0.86–1.02
0.86–1.48
0.69–1.26
0.40–3.54
NE*
0.17–3.42
0.55–1.63
0.34–1.05
CI, confidence interval; NE, not estimable.
Bold indicates statistically significant results.
VOL. 112, NO. 1, JULY 2008
Dodd et al
Progesterone for Preterm Birth
131
Progesterone Versus Placebo for Women After
Presentation with Threatened Preterm Labor
Primary Outcomes: For women administered progesterone during pregnancy, for the primary outcomes
perinatal death and preterm birth at less than 34
weeks of gestation, there were no statistically significant differences identified when compared with
placebo.
Secondary Infant Outcomes: For women administered
progesterone during pregnancy, when compared with
placebo, there was a statistically significant reduction in
the risk of infant birth weight less than 2,500 g (one
study, 70 infants, RR 0.52, 95% CI 0.28 – 0.98, number
needed to treat to benefit 5, 95% CI 2– 45) and respiratory distress syndrome (one study, 70 infants, RR 0.30,
95% CI 0.11– 0.83, number needed to treat to benefit 5,
95% CI 2– 45). There were no statistically significant
differences for the outcomes need for mechanical ventilation or sepsis.
Secondary Maternal Outcomes: For women administered progesterone during pregnancy, when compared with placebo, there was a statistically significant
reduction in the risk of preterm birth at less than 37
weeks (one study, 60 women, RR 0.29, 95% CI
0.12– 0.69, number needed to treat to benefit 3, 95%
CI 2– 6).
Route of Administration, Time of Commencing Therapy, and Dose of Progesterone: It was not possible to
assess the effect of route of progesterone administration, gestational age at commencement of therapy, or
total cumulative dose of medication.
Progesterone Versus Placebo for Women With
“Other” Risk Factors for Preterm Birth
Primary Outcomes: For women administered progesterone during pregnancy, for the primary outcome perinatal death, there were no statistically significant
differences identified when compared with placebo
(two studies, 264 participants, RR 1.10, 95% CI
0.23–5.29).
Secondary Infant Outcomes: There were no statistically significant differences for the outcomes perinatal
death, infant birth weight less than 2,500 g, intrauterine fetal death, or neonatal death.
Secondary Maternal Outcomes: There were no statistically significant differences for the outcome preterm
birth at less than 37 weeks of gestation.
Route of Administration, Time of Commencing Therapy, and Dose of Progesterone: There was no differential
effect observed related to cumulative dose of progesterone administered or gestational age at commencement of therapy.
132
Dodd et al
Progesterone for Preterm Birth
CONCLUSION
The randomized trials identified assessed the use of
progesterone in women considered to be at increased
risk of preterm birth due to a variety of risk factors.
For women with a past history of spontaneous
preterm birth, there was a significant reduction in the
risk of preterm birth at less than 34 weeks demonstrated in one study. There were no statistically significant differences identified for the primary outcome perinatal death. Further information is required
about the optimal route of administration of progesterone, with the largest study to date using vaginal
progesterone gel suggesting no benefit in this group of
women.36 There are three ongoing randomized trials
assessing the role of intramuscular (P. Rozenberg,
e-mail communication, February 14, 2008) and vaginal (C.A. Crowther, J.M. Dodd, A.J. McPhee, V.
Flenady, e-mail communication, February 14, 2008;
Y. Perlitz, e-mail communication, February 14, 2008)
progesterone in women with a history of spontaneous
preterm birth, which will contribute information
about the role of progesterone in this group of women.
In the single trial to date assessing the role of
progesterone in women with a short cervix identified
on ultrasound,31 there were no statistically significant
differences identified for the primary outcome perinatal death. Women administered progesterone were
significantly less likely to have preterm birth at less
than 34 weeks of gestation, although further information is required about the risk of other infant and
maternal health outcomes in this group of women.
There is a single ongoing randomized trial assessing
the role of intramuscular (W. Gorbman, e-mail communication, February 14, 2008) progesterone in nulliparous women with short cervices identified on
transvaginal ultrasound, which will contribute information in the future.
The role of progesterone in women with a multiple pregnancy is less clear, with no identified differences in the primary outcomes perinatal death and
preterm birth at less than 34 weeks of gestation.
Although the use of progesterone was associated with
a reduction in the use of antenatal tocolysis, there
were no differences identified for the other secondary
infant and maternal health outcomes. There are several ongoing randomized trials assessing the role of
intramuscular (H.W. Bruinse, e-mail communication,
February 14, 2008; K. Maurel, A. Combs, e-mail
communication, February 14, 2008; A. Nassar, e-mail
communication, February 14, 2008) and vaginal (L.
Rode, e-mail communication, February 14, 2008; V.
Serra, e-mail communication, February 14, 2008; S.
OBSTETRICS & GYNECOLOGY
Wood, e-mail communication, February 14, 2008)50
progesterone in women with a multiple pregnancy.
The role of progesterone for women after presentation with threatened preterm labor remains uncertain because the combined sample size of these
studies was small and underpowered to detect differences in both maternal and infant health outcomes.29,38 Furthermore, the failure to use a placebo
and lack of blinding in the assessment of outcomes
increases the potential for bias. There is an ongoing
randomized trial assessing the role of vaginal progesterone (B. Matrinez de Tajada, e-mail communication, February 14, 2008) in women presenting with
symptoms or signs of threatened preterm labor, which
will contribute information in the future.
The role of progesterone in women considered to
be at risk of preterm birth for “other” reasons is
uncertain, with the two randomized trials to date
indicating no benefit in terms of perinatal death or
preterm birth.33,37 However, the combined sample
size of these two trials is underpowered to detect all
but large differences in these outcomes.
There remains limited information about the
benefits and harms of progesterone, particularly in
relation to long-term outcomes for the infants. Information is available from the follow-up of a single
randomized trial related to long-term infant and childhood health outcomes.39 Although this report indicates no statistically significant differences in health
and developmental assessment at 2 years of age,39
ongoing assessment of participants in randomized
trials remains a priority. Maternal outcomes after
antenatal progesterone therapy, including treatment
side effects, preferences of mode of administration,
and satisfaction with care, were poorly reported in the
available literature. Further information is required
on these important issues.51,52 Uncertainty remains
about the optimal dose, route of administration,
and gestational age at which to commence progesterone therapy. The American College of Obstetricians and Gynecologists has issued a statement
indicating the need for further information about
the optimal mode of administration.53 To date only
three studies have been reported detailing the use
of vaginal progesterone therapy.30,31,36 Further information is required from randomized trials relating to the effect of vaginal progesterone on maternal and infant health outcomes for women at risk of
preterm birth.
Progesterone is associated with some beneficial
effects in pregnancy outcome for some women at increased risk of preterm birth. Over time, the results of
current randomized trials will assist in further elucidat-
VOL. 112, NO. 1, JULY 2008
ing the precise role of progesterone therapy for women
considered to be at increased risk of preterm birth.
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