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Reviews

Progesterone for the Prevention of PretermBirthA Systematic Review

Jodie M. Dodd, PhD, FRANZCOG, Vicki J. Flenady, RN, MPH, Robert Cincotta, FRANZCOG,and Caroline A. Crowther, MD, FRANZCOG

OBJECTIVE: We performed a systematic review to assessthe benefits and harms of progesterone administrationfor the prevention of preterm birth in women and theirinfants.

DATA SOURCES: The Cochrane Controlled Trials Regis-

ter was searched, and reference lists of retrieved studieswere searched by hand. No date or language restrictionswere placed.

METHODS OF STUDY SELECTION: Randomized trialscomparing antenatal progesterone for women at risk ofpreterm birth were considered. Studies were evaluatedfor inclusion and methodological quality. Primary out-comes were perinatal death, preterm birth before 34weeks, and neurodevelopmental handicap.

TABULATION, INTEGRATION AND RESULTS: Elevenrandomized controlled trials (2,425 women and 3,187infants) were included. For women with a history of

spontaneous preterm birth, progesterone was associatedwith a significant reduction in preterm birth before 34weeks (one study, 142 women, RR 0.15, 95% CI 0.040.64, number needed to treat 7, 95% CI 417), but nostatistically significant differences were identified for theoutcome of perinatal death. For women with a shortcervix identified on ultrasound, progesterone was notassociated with a significant difference in perinatal death

(one study, 274 participants, RR 0.38, 95% CI 0.101.40),

but there was a significant reduction in preterm birth

before 34 weeks (one study, 250 women, RR 0.58, 95% CI

0.380.87, number needed to treat 7, 95% CI 425). For

women with a multiple pregnancy, progesterone was

associated with no significant difference in perinataldeath (one study, 154 participants, RR 1.95, 95% CI

0.3710.33). For women presenting after threatened pre-

term labor, no primary outcomes were reported. For

women with other risk factors for preterm birth, pro-

gesterone was not associated with a significant differencein perinatal death (two studies, 264 participants, RR 1.10,95% CI 0.235.29).

CONCLUSION: Progesterone is associated with somebeneficial effects in pregnancy outcome for some womenat increased risk of preterm birth.(Obstet Gynecol 2008;112:12734)

Preterm birth, defined by the World Health Orga-nization as birth before 37 completed weeks of

gestation,1 is estimated to affect approximately 13million births annually worldwide.2 The incidence ofpreterm 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% inAustralia,7 and 12.7% in the United States.8 Theprevention of preterm birth remains elusive, withmany reports indicating an increase in prevalenceduring recent years.911

Infants who are born preterm are more likely to

die during the neonatal period than are term in-fants,12,13 and although the risk is greatest for infantsborn at earlier gestational ages, it remains evident forinfants born between 32 and 36 weeks of gestation.14

For surviving infants, the health implications of im-maturity are significant, particularly in relation torespiratory distress syndrome,15 and the subsequentrisk of developing chronic lung disease,16 and otherlong-term handicaps including cerebral palsy.17

From the Discipline of Obstetrics and Gynaecology, the University of Adelaide,Adelaide, South Australia, Australia; the Centre for Clinical Research, theMater Mothers Hospital, Brisbane, Australia; and the Mater Mothers Hospital,Brisbane, Australia.

Supported by the Australian National Health and Medical Research CouncilNeil Hamilton Fairley Overseas Clinical Fellowship (ID 399224) to Dr. Dodd.

Corresponding author: Dr. Jodie Dodd, the University of Adelaide, Discipline ofObstetrics & Gynaecology, Womens and Childrens Hospital, 72 King WilliamRoad, North Adelaide, South Australia 5006, Australia; e-mail: [email protected].

Financial Disclosure

The authors have no potential conflicts of interest to disclose.

2008 by The American College of Obstetricians and Gynecologists. Publishedby Lippincott Williams & Wilkins.

ISSN: 0029-7844/08

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The cause of preterm birth is multifactorial, withthe most significant and consistently identified riskfactor being a womans history of previous pretermbirth.1821 Other characteristics in a womans currentpregnancy placing her at increased risk of pretermbirth include the identification of short cervix byultrasound assessment and multiple pregnancy.

Progesterone has a role in maintaining preg-

nancy2224 and is thought to act by suppressing smoothmuscle activity in the uterus.25,26 We performed asystematic review to assess the benefits and harms ofprogesterone administration for the prevention ofpreterm birth in women and their infants.

SOURCESWe searched PubMed, the Cochrane Controlled Tri-als Register, and the International Clinical TrialsRegister using the free text search terms pregnancy,preterm birth, progesterone, progestogen, intramus-

cular, vaginal, oral, perinatal morbidity, perinatalmortality, and randomis(z)ed controlled trial. Thereference lists of retrieved studies were searched byhand, and no date or language restrictions wereplaced (date of last search was January 2008).

STUDY SELECTIONAll published randomized controlled trials in whichprogesterone was administered for the prevention ofpreterm birth were considered. Studies were subdi-vided by reason the women were considered to be atrisk for preterm birth, including past history of spon-

taneous preterm birth (including preterm prematurerupture of membranes), multiple pregnancy, ultra-sound-identified short cervical length, and after pre-sentation with symptoms or signs of threatened pre-term labor. Trials were excluded if progesterone wasadministered for the treatment of actual or threatenedpreterm labor, if progesterone was administered forpreventing miscarriage, or if studies were available inabstract form only.

The primary outcomes were perinatal mortality,preterm birth before 34 weeks of gestation, anddevelopmental delay in childhood. The secondary

outcomes included threatened preterm labor, cesar-ean section, antenatal corticosteroids, use of antenataltocolysis, preterm birth at less than 37 weeks ofgestation, infant birth weight less than 2,500 g, respi-ratory distress syndrome, need for assisted ventila-tion, intraventricular hemorrhage, retinopathy of pre-maturity, necrotizing enterocolitis, neonatal sepsis(either culture-proven or presumptive), patent ductusarteriosus, fetal death, and neonatal death.

Studies under consideration were evaluated inde-pendently for appropriateness for inclusion and meth-odological quality without consideration of their re-sults by all authors, according to the QUOROMguidelines for systematic reviews of randomized tri-als.27 There was no blinding of authorship.

Assessment of quality considered generation ofthe randomization sequence, allocation concealment,

blinding, and completeness of follow up. We definedhigh-quality trials as those receiving an A rating forblinding of randomization, blinding of the interven-tion, and less than 20% loss to follow-up for majoroutcomes. For dichotomous data, relative risks (RRs)and 95% confidence intervals (CIs) were calculated.Primary analyses were based on intention to treatprinciples. Planned subgroup analyses included anassessment of the effect of 1) time of treatmentcommencing (before 20 weeks of gestation versusafter 20 weeks of gestation), 2) route of administration(intramuscular, intravaginal, oral, intravenous), and 3)

different dosage regimens (divided arbitrarily into acumulative dose of less than 500 mg per week and adose of greater than or equal to 500 mg per week).

Twenty-two studies were identified for consider-ation. Eleven studies met the inclusion criteria.2838

For use of progesterone in women with a historyof prior spontaneous preterm birth, four studies wereincluded, involving 1,307 women with a past historyof spontaneous preterm birth.30,3436 Two of these com-pared weekly intramuscular injection with placebo,34,35

and two compared nightly vaginal progesterone withplacebo.30,36 The primary outcomes reported related

to preterm birth before 32 weeks of gestation36 and 37weeks of gestation.30,34,35 The report by Northen39

details the 2-year follow-up of 278 participants fromthe Meis randomized trial.35

Intramuscular ProgesteroneThe method of generating the randomization se-quence was adequate in one study,35 with both studiesusing identical-appearing treatment packs (allocationconcealment: A),34,35 and blinding of outcome assess-ment (blinding: A).34,35 There were no reported lossesto follow-up in the study by Meis35 and 14% postran-

domization exclusions in the study by Johnson.34 Bothtrials received a quality rating of A.

Vaginal ProgesteroneThe method of generating the randomization se-quence was adequate in both studies,30,36 both usingsequentially numbered identical-appearing treatmentpacks (allocation concealment: A) and blinded out-come assessors (blinding: A).30,36 Both studies re-

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ported less than 20% loss to follow-up (DaFonesca10%, OBrien 7.3%),30,36 and received a quality ratingof A.

For use of progesterone in women with a shortcervix identified on transvaginal ultrasound examina-tion, a single study was included involving 250women who were identified as having short cervix(defined as less than 15 mm) at the time of transvag-

inal ultrasound examination.31 Women received ei-ther 200 mg nightly intravaginal progesterone orplacebo from 24 to 33 completed weeks of gestation.The primary outcome related to the occurrence ofpreterm birth before 34 weeks of gestation.

Vaginal ProgesteroneThe method of generating the randomization se-quence was not stated.31 The study used centralrandomization with identical-appearing treatmentpacks (allocation concealment: A) and blinded out-come assessors (blinding: A).31 There were no re-

ported losses to follow-up. The trial received a qualityrating of A.

For use of progesterone in women with a multiplepregnancy, two studies were included, involving 738women with a twin pregnancy28,32 who receivedweekly intramuscular injections in a dose of 250 mgor placebo. The primary outcomes reported includeda composite of death or birth before 35 weeks ofgestation.28

Intramuscular ProgesteroneHartikainen32 did not indicate the method of genera-

tion of the randomization sequence or allocationconcealment (allocation concealment: B) but indi-cated the use of blinded outcome assessors (blinding:A) and reported no losses to follow-up, receiving anoverall quality rating of B. The trial by Rouse28

indicated the method of generation of the randomiza-tion sequence, used identical-appearing treatmentpacks (allocation concealment: A), used blinded out-come assessors (blinding: A), reported 1% loss tofollow-up, and received an overall quality rating of A.

For use of progesterone in women after symp-toms or signs of threatened preterm labor, two studies

involving 130 women presenting with symptoms orsigns of threatened preterm labor (including bothuterine contraction pattern and evidence of cervicalchange) between 2425 and 34 weeks of gestationwere included, in which women were randomizedafter the use of acute tocolysis to arrest uterineactivity.29,38 In the study by Borna,29 women receivedeither vaginal progesterone pessaries on a daily basis(400 mg) from randomization until birth or no treat-

ment. The primary outcome reported was the intervalfrom randomization to birth. In the study by Fachi-netti,38 women received either intramuscular proges-terone (341 mg) every 4 days from randomizationuntil 36 weeks of gestation or no treatment. Theprimary outcome reported was transvaginal ultra-sound detection of short cervical length.

Intramuscular ProgesteroneThe study by Fachinetti38 used a random numbertable to generate the randomization sequence, whichwas managed by a senior midwife (allocation conceal-ment: B). The study did not use blinded outcomeassessors (blinding: B), reported no losses to follow-up, and received a quality rating of B.

Vaginal ProgesteroneThe study by Borna29 used a random number table togenerate the randomization sequence. There was noindication of the method of allocation concealment

(allocation concealment: B) and the study did not useblinded outcome assessors (blinding: B) and reportedno losses to follow-up. The trial received a qualityrating of B.

For use of progesterone in women at risk ofpreterm birth for other reasons, the study by Pa-piernik37 recruited 99 women with a high pretermrisk score. Women were allocated to receive eitherintramuscular progesterone three times per week orplacebo.

The study by Hauth33 involved 168 women whowere considered to be at risk of preterm birth because

of active military service. Women received either1,000 mg of intramuscular progesterone weekly orplacebo. The primary outcome for the study relatedto the incidence of preterm birth at less than 37 weeksof gestation.

Intramuscular ProgesteroneNeither study33,37 indicated the method of randomiza-tion used or the process of allocation concealment(allocation concealment: B), but both stated the use ofblinded outcome assessors (blinding: A) and reportedno 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.4042

One study43 compared an oral progestogen withplacebo but presented outcomes only as percentages.Five studies were excluded because progesterone wasadministered in the first trimester to prevent miscar-riage.4448 One study comparing progesterone withcervical cerclage49 has been reported in abstract form

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only but was not included because insufficient infor-mation was presented.

RESULTSEleven randomized controlled trials involving a totalof 2,425 women and 3,187 infants were included inthe meta-analysis.

Progesterone Compared With Placebo forWomen With a Past History of SpontaneousPreterm BirthPrimary Outcomes:For women administered progester-one during pregnancy, for the primary outcomesperinatal death and developmental delay in child-hood, there were no statistically significant differencesidentified when compared with placebo. Womenadministered progesterone were significantly lesslikely to have a preterm birth at less than 34 weeks ofgestation (one study, 142 women, RR 0.15, 95% CI0.040.64, number needed to treat to benefit 7, 95%

CI 417). See Table 1.Secondary Infant Outcomes: For women adminis-

tered progesterone during pregnancy, when comparedwith placebo, there was a statistically significant reduc-tion in the risk of infant birth weight less than 2,500 g

(two studies, 501 infants, RR 0.64, 95% CI 0.490.83,number needed to treat to benefit 7, 95% CI 517).

Secondary Maternal Outcomes:There were no statis-tically significant differences for the secondary mater-nal outcomes reported.

Route of Administration, Time of Commencing Ther-apy, and Dose of Progesterone:There was no differentialeffect on the outcomes when considering route of

administration of progesterone, time of commence-ment of supplementation, or total weekly cumulativedose of progesterone.

Progesterone Versus Placebo for Women Witha Short Cervix Identified on UltrasoundPrimary Outcomes:For women administered progester-one during pregnancy, for the primary outcome peri-natal death, there were no statistically significantdifferences identified when compared with placebo.Women administered progesterone were significantlyless 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 benefit7, 95% CI 4 25). See Table 2.

Secondary Infant Outcomes:For women administeredprogesterone during pregnancy, when compared with

Table 1. Progesterone Versus Placebo in Women With a Prior Spontaneous Preterm Birth

Outcome No. Studies Participants Relative Risk 95% CI

PrimaryPerinatal death 3 1,114 0.65 0.381.11Preterm birth at less than 34 wk 1 142 0.15 0.040.64

Developmental delay* 1 275 0.97 0.551.73Secondary maternal

Threatened preterm labor 2 601 0.87 0.471.62Cesarean delivery 2 1,070 1.01 0.821.23Antenatal corticosteroids 2 1,070 0.92 0.731.16Antenatal tocolysis 3 1,114 1.11 0.811.52

Secondary infantPreterm birth at less than 37 wk 4 1,255 0.68 0.451.02Birthweight less than 2,500 g 2 501 0.64 0.490.83Respiratory distress syndrome 2 1,069 0.79 0.571.10Need for assistedventilation 1 459 0.59 0.351.01Intraventricular hemorrhage, all grades 2 1,070 0.54 0.122.47Intraventricular hemorrhage, grade 3 or 4Retinopathy of prematurity 2 1,069 1.59 0.2111.75

Necrotizing enterocolitis

Neonatal sepsis 1 458 0.50 0.151.69Patent ductus arteriosus 2 1,070 0.25 0.032.46Fetal death 1 459 1.13 0.353.59Neonatal death 1 459 0.44 0.161.18

3 1,114 0.85 0.352.033 1,114 0.56 0.281.10

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.

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placebo, there was a statistically significant reduction inthe risk of neonatal sepsis (one study, 274 infants, RR0.28, 95% CI 0.080.97, number needed to treat to

benefit 18, 95% CI 9163), but no other differenceswere identified for other secondary infant outcomes.

Route of Administration, Time of Commencing Ther-apy, and Dose of Progesterone: It was not possible toassess the effect of route of progesterone administra-tion, gestational age at commencement of therapy, ortotal cumulative dose of medication.

Progesterone Versus Placebo for Women Witha Multiple PregnancyPrimary Outcomes:For women administered progester-one during pregnancy, for the primary outcomes

perinatal death and preterm birth at less than 34weeks of gestation, there were no statistically signifi-

cant differences identified when compared with pla-cebo. See Table 3.

Secondary Infant Outcomes:For women administered

progesterone during pregnancy, when compared withplacebo, there were no statistically significant differencesfor the reported secondary infant outcomes.

Secondary Maternal Outcomes:For women adminis-tered progesterone during pregnancy, when com-pared with placebo, there was a statistically significantreduction in the need for antenatal tocolysis (onestudy, 654 women, RR 0.75, 95% CI 0.57 0.97,number needed to treat to benefit 14, 95% CI 8123).

Route of Administration, Time of Commencing Ther-apy, and Dose of Progesterone:There was no differential

effect observed when considering time of commence-ment of supplementation.

Table 2. Progesterone Versus Placebo in Women With a Short Cervix Identified on Ultrasound


PrimaryPerinatal death 1 274 0.38 0.101.40Preterm birth at less than 34 wk 1 250 0.58 0.380.87

Secondary infantBirth weight less than 2,500 g 1 274 0.96 0.731.27Respiratory distress syndrome 1 274 0.59 0.291.19

Need for assisted ventilation 1 274 0.65 0.361.16Intraventricular hemorrhage, all grades 1 274 0.51 0.055.53Retinopathy of prematurity 1 274 5.07 0.25104.70Necrotizing enterocolitis 1 274 0.34 0.018.23Neonatal sepsis 1 274 0.28 0.080.97Fetal death 1 274 1.01 0.0616.06Neonatal Death 1 274 0.29 0.061.37

CI, confidence interval.Bold indicates statistically significant results.

Table 3. Progesterone Versus Placebo in Women With a Multiple Pregnancy


PrimaryPerinatal death 1 154 1.95 0.3710.33

Secondary maternalCesarean section 1 652 0.99 0.881.12Antenatal corticosteroids 1 654 0.91 0.701.17Antenatal tocolysis 1 654 0.75 0.570.97

Secondary infant

Preterm birth at less than 37 wk 2 732 1.01 0.921.12Birth weight less than 2,500 g 1 1,276 0.94 0.861.02Respiratory distress syndrome 1 1,280 1.13 0.861.48Need for assisted ventilation 1 1,280 0.93 0.691.26Intraventricular hemorrhage, grades 3 or 4 1 1,280 1.20 0.403.54Retinopathy of prematurity 1 1,280 NE* NE*Necrotizing enterocolitis 1 1,280 0.77 0.173.42Neonatal sepsis 1 1,280 0.95 0.551.63Patent ductus arteriosus 1 1,280 0.60 0.341.05

CI, confidence interval; NE, not estimable.Bold indicates statistically significant results.


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Progesterone Versus Placebo for Women AfterPresentation with Threatened Preterm LaborPrimary Outcomes:For women administered progester-one during pregnancy, for the primary outcomesperinatal death and preterm birth at less than 34weeks of gestation, there were no statistically signifi-cant differences identified when compared withplacebo.

Secondary Infant Outcomes:For women administeredprogesterone during pregnancy, when compared withplacebo, there was a statistically significant reduction inthe risk of infant birth weight less than 2,500 g (onestudy, 70 infants, RR 0.52, 95% CI 0.280.98, numberneeded to treat to benefit 5, 95% CI 245) and respira-tory distress syndrome (one study, 70 infants, RR 0.30,95% CI 0.110.83, number needed to treat to benefit 5,95% CI 245). There were no statistically significantdifferences for the outcomes need for mechanical ven-tilation or sepsis.

Secondary Maternal Outcomes:For women adminis-tered progesterone during pregnancy, when com-pared with placebo, there was a statistically significantreduction in the risk of preterm birth at less than 37weeks (one study, 60 women, RR 0.29, 95% CI0.120.69, number needed to treat to benefit 3, 95%CI 26).

Route of Administration, Time of Commencing Ther-apy, and Dose of Progesterone: It was not possible toassess the effect of route of progesterone administra-tion, gestational age at commencement of therapy, ortotal cumulative dose of medication.

Progesterone Versus Placebo for Women WithOther Risk Factors for Preterm BirthPrimary Outcomes:For women administered progester-one during pregnancy, for the primary outcome peri-natal death, there were no statistically significantdifferences identified when compared with placebo(two studies, 264 participants, RR 1.10, 95% CI0.235.29).

Secondary Infant Outcomes:There were no statisti-cally significant differences for the outcomes perinataldeath, infant birth weight less than 2,500 g, intrauter-

ine fetal death, or neonatal death.Secondary Maternal Outcomes:There were no statis-

tically significant differences for the outcome pretermbirth at less than 37 weeks of gestation.

Route of Administration, Time of Commencing Ther-apy, and Dose of Progesterone:There was no differentialeffect observed related to cumulative dose of proges-terone administered or gestational age at commence-ment of therapy.

CONCLUSIONThe randomized trials identified assessed the use ofprogesterone in women considered to be at increasedrisk of preterm birth due to a variety of risk factors.

For women with a past history of spontaneouspreterm birth, there was a significant reduction in therisk of preterm birth at less than 34 weeks demon-strated in one study. There were no statistically sig-nificant differences identified for the primary out-come perinatal death. Further information is requiredabout the optimal route of administration of proges-terone, with the largest study to date using vaginalprogesterone gel suggesting no benefit in this group ofwomen.36 There are three ongoing randomized trialsassessing the role of intramuscular (P. Rozenberg,e-mail communication, February 14, 2008) and vagi-nal (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 spontaneouspreterm birth, which will contribute informationabout the role of progesterone in this group of women.

In the single trial to date assessing the role ofprogesterone in women with a short cervix identifiedon ultrasound,31 there were no statistically significantdifferences identified for the primary outcome peri-natal death. Women administered progesterone weresignificantly less likely to have preterm birth at lessthan 34 weeks of gestation, although further informa-tion is required about the risk of other infant andmaternal health outcomes in this group of women.

There is a single ongoing randomized trial assessingthe role of intramuscular (W. Gorbman, e-mail com-munication, February 14, 2008) progesterone in nul-liparous women with short cervices identified ontransvaginal ultrasound, which will contribute infor-mation in the future.

The role of progesterone in women with a mul-tiple pregnancy is less clear, with no identified differ-ences in the primary outcomes perinatal death andpreterm birth at less than 34 weeks of gestation.Although the use of progesterone was associated witha reduction in the use of antenatal tocolysis, there

were no differences identified for the other secondaryinfant and maternal health outcomes. There are sev-eral ongoing randomized trials assessing the role ofintramuscular (H.W. Bruinse, e-mail communication,February 14, 2008; K. Maurel, A. Combs, e-mailcommunication, February 14, 2008; A. Nassar, e-mailcommunication, February 14, 2008) and vaginal (L.Rode, e-mail communication, February 14, 2008; V.Serra, e-mail communication, February 14, 2008; S.

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Wood, e-mail communication, February 14, 2008)50

progesterone in women with a multiple pregnancy.The role of progesterone for women after presen-

tation with threatened preterm labor remains uncer-tain because the combined sample size of thesestudies was small and underpowered to detect differ-ences in both maternal and infant health out-comes.29,38 Furthermore, the failure to use a placebo

and lack of blinding in the assessment of outcomesincreases the potential for bias. There is an ongoingrandomized trial assessing the role of vaginal proges-terone (B. Matrinez de Tajada, e-mail communica-tion, February 14, 2008) in women presenting withsymptoms or signs of threatened preterm labor, whichwill contribute information in the future.

The role of progesterone in women considered tobe at risk of preterm birth for other reasons isuncertain, with the two randomized trials to dateindicating no benefit in terms of perinatal death orpreterm birth.33,37 However, the combined sample

size of these two trials is underpowered to detect allbut large differences in these outcomes.

There remains limited information about thebenefits and harms of progesterone, particularly inrelation to long-term outcomes for the infants. Infor-mation is available from the follow-up of a singlerandomized trial related to long-term infant and child-hood health outcomes.39 Although this report indi-cates no statistically significant differences in healthand developmental assessment at 2 years of age,39

ongoing assessment of participants in randomizedtrials remains a priority. Maternal outcomes after

antenatal progesterone therapy, including treatmentside effects, preferences of mode of administration,and satisfaction with care, were poorly reported in theavailable literature. Further information is requiredon these important issues.51,52 Uncertainty remainsabout the optimal dose, route of administration,and gestational age at which to commence proges-terone therapy. The American College of Obstetri-cians and Gynecologists has issued a statementindicating the need for further information aboutthe optimal mode of administration.53 To date onlythree studies have been reported detailing the use

of vaginal progesterone therapy.30,31,36 Further in-formation is required from randomized trials relat-ing to the effect of vaginal progesterone on mater-nal and infant health outcomes for women at risk ofpreterm birth.

Progesterone is associated with some beneficialeffects in pregnancy outcome for some women at in-creased risk of preterm birth. Over time, the results ofcurrent randomized trials will assist in further elucidat-

ing the precise role of progesterone therapy for womenconsidered to be at increased risk of preterm birth.

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