Progesterone for the Prevention of Preterm Birth Paul Meis MD.

Progesterone for Progesterone for the Prevention of the Prevention of

Preterm BirthPreterm Birth

Paul Meis MD Paul Meis MD

Preterm Delivery: Current StatusPreterm Delivery: Current Status Overview of the problem of preterm birthOverview of the problem of preterm birth

Strategies to prevent preterm deliveryStrategies to prevent preterm delivery

Progesterone for prevention of preterm Progesterone for prevention of preterm birthbirth

Early trialsEarly trials

NICHD MFMU Network trialNICHD MFMU Network trial

Preterm Births in United StatesPreterm Births in United States

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

Preterm Births by RacePreterm Births by Race



Very Low Birthweight BirthsVery Low Birthweight Births



Costs of PrematurityCosts of Prematurity

Preterm birth is the major Preterm birth is the major determinant of infant mortality in determinant of infant mortality in developed countries developed countries

Preterm birth is a leading cause of Preterm birth is a leading cause of cerebral palsy and developmental cerebral palsy and developmental delay of surviving childrendelay of surviving children

Costs of PrematurityCosts of Prematurity

The Institute of Medicine estimates that The Institute of Medicine estimates that the total national cost of preterm birth to the total national cost of preterm birth to be $26.2 billion at a minimum.be $26.2 billion at a minimum.

Initial hospital care of infants born at 25-Initial hospital care of infants born at 25-27 weeks costs 28 times as much as for 27 weeks costs 28 times as much as for those born at termthose born at term

Costs of PrematurityCosts of PrematuritySchool Performance Age 9-11School Performance Age 9-11

0

1

2

3

4

5

6

7

8

Reading Difficuties Spelling Difficulties

33-3637-3839-40

Kirkegaard I, Pediatrics

Kirkegaard I, Pediatrics 2006;118:1600

“…“…effective therapeutic effective therapeutic interventions to decrease interventions to decrease spontaneous preterm delivery spontaneous preterm delivery have not been discovered.”have not been discovered.”

R.L. Goldenberg 2002R.L. Goldenberg 2002

Progesterone Treatment: Progesterone Treatment: An Old Idea RevisitedAn Old Idea Revisited

A trial of 17 alpha Hydroxyprogesterone A trial of 17 alpha Hydroxyprogesterone Caproate (17P) conducted in the NICHD Caproate (17P) conducted in the NICHD Maternal Fetal Medicine Units Network.Maternal Fetal Medicine Units Network.

A trial of progesterone suppositories A trial of progesterone suppositories conducted in Brazil.conducted in Brazil.

Actions of Progesterone on the Actions of Progesterone on the MyometriumMyometrium

Decreases conduction of contractionsDecreases conduction of contractions Increases threshold for stimulationIncreases threshold for stimulation Decreases spontaneous activityDecreases spontaneous activity Decreases number of oxytocin Decreases number of oxytocin

receptorsreceptors Suppresses the inflammatory cascadeSuppresses the inflammatory cascade

Actions of Progesterone on the Actions of Progesterone on the MyometriumMyometrium

Inhibits T lymphocyte developmentInhibits T lymphocyte development Promotes expression of prostaglandin EPPromotes expression of prostaglandin EP22

receptorreceptor Prevents formation of gap junctionsPrevents formation of gap junctions Administration of progesterone Administration of progesterone

antagonists stimulates onset of labor in antagonists stimulates onset of labor in women at termwomen at term

Early Trials of ProgesteroneEarly Trials of Progesterone

Patients with symptoms of preterm labor in 1956-Patients with symptoms of preterm labor in 1956-1957, University of Copenhagen1957, University of Copenhagen

Double blind study of progesterone (N = 63) vs Double blind study of progesterone (N = 63) vs placebo (N = 63)placebo (N = 63)

Daily dose was 200mg x3, 150mg x2, then 100mg Daily dose was 200mg x3, 150mg x2, then 100mg per dayper day

Results showed no efficacy to prolong pregnancyResults showed no efficacy to prolong pregnancy ““Progesterone unable to prevent PTD once clinical Progesterone unable to prevent PTD once clinical

symptoms are present”symptoms are present”

Fuchs F, AJOG 1960 79:172


Selected 99 women who were at risk for Selected 99 women who were at risk for preterm delivery using a high risk scoring preterm delivery using a high risk scoring system and randomized them to treatment system and randomized them to treatment with 17P or placebowith 17P or placebo

Treated with 250 mg 17P or placebo every Treated with 250 mg 17P or placebo every three days from 28-32 weeks for a total of 8 three days from 28-32 weeks for a total of 8 dosesdoses

Delivery at <37 weeks’ in 4% of the 17P Delivery at <37 weeks’ in 4% of the 17P group and 18% of the placebo groupgroup and 18% of the placebo group

Papiernik E, 1970


43 patients with previous recurrent 43 patients with previous recurrent miscarriage or preterm birthmiscarriage or preterm birth

Treated with 17P or placeboTreated with 17P or placebo 41% of placebo group delivered <36 41% of placebo group delivered <36

weeks of pregnancyweeks of pregnancy All of treated group delivered after 36 All of treated group delivered after 36

weeksweeks

Johnson JWC. NEJM 1975;293:675-680


168 pregnant women in the military168 pregnant women in the military Treated with 17P or placeboTreated with 17P or placebo Low birth weight infants:Low birth weight infants:

7.5% in treated subjects7.5% in treated subjects 9.0% in placebo subjects9.0% in placebo subjects

Hauth JC. Am J Obstet Gynecol 1983;146:187


77 women with twin pregnancies, randomized 77 women with twin pregnancies, randomized to weekly injections of 250 mg 17P or placeboto weekly injections of 250 mg 17P or placebo

Started after 28 weeks and continued to 37 Started after 28 weeks and continued to 37 weeksweeks

Delivery at <37 weeks in 31% of the 17P Delivery at <37 weeks in 31% of the 17P group and 24% of the placebo groupgroup and 24% of the placebo group

This is the only reported trial of 17P in twinsThis is the only reported trial of 17P in twins

Hartikainen A. Obstet Gynecol 1980;56:692

Meta-analysis of progesterone Meta-analysis of progesterone use in pregnancyuse in pregnancy

15 published trials of various 15 published trials of various progesterone compounds in women at progesterone compounds in women at high riskhigh risk

Pooled analysis of the results of the Pooled analysis of the results of the trials showed no effect on rates of:trials showed no effect on rates of: MiscarriageMiscarriage StillbirthsStillbirths Preterm birthsPreterm births

Goldstein P. Brit J Obstet Gynecol 1989;96:265

Meta-analysis of 17P in Meta-analysis of 17P in pregnancypregnancy

5 trials which treated high risk women 5 trials which treated high risk women with 17Pwith 17P

Pooled analysis of results showed:Pooled analysis of results showed: Reduction in rates of preterm birth. Reduction in rates of preterm birth.

Odds ratio was 0.50, 95% CI: 0.30-0.85Odds ratio was 0.50, 95% CI: 0.30-0.85 Reduction in rates of low birthweight, Reduction in rates of low birthweight,

Odds ratio was 0.46, 95% CI: 0.27-0.80Odds ratio was 0.46, 95% CI: 0.27-0.80

Keirse MJNC. Brit J Obstet Gynecol 1990;97:149

““The present study indicates that The present study indicates that injections of (17P) may reduce the injections of (17P) may reduce the occurrence of preterm birth in women occurrence of preterm birth in women so treated.”so treated.”

“… “… further well-controlled research further well-controlled research would be necessary before it is would be necessary before it is recommended for clinical practice.”recommended for clinical practice.”

Keirse MJNC. Brit J Obstet Gynecol 1990;97:149

The existence of the NICHD The existence of the NICHD supported MFMU Network supported MFMU Network

made such a large well-made such a large well-controlled trial possiblecontrolled trial possible

PreventionPrevention of Recurrent of Recurrent Preterm Delivery by 17 Alpha-Preterm Delivery by 17 Alpha-

Hydroxyprogesterone CaproateHydroxyprogesterone Caproate

Meis PJ, Klebanoff M, Thom E, Dombrowski M P, Sibai B, Moawad AH, Meis PJ, Klebanoff M, Thom E, Dombrowski M P, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, and Peaceman AM for the NICHD MFMUNB, Ramin SM, Thorp JM, and Peaceman AM for the NICHD MFMUN

NEJM 2003;348:2379-85.NEJM 2003;348:2379-85.

Participating Centers of the MFMU NetworkParticipating Centers of the MFMU Network Wake Forest UniversityWake Forest University University of TennesseeUniversity of Tennessee University of Alabama-University of Alabama-

BirminghamBirmingham University of UtahUniversity of Utah Magee-Womens HospitalMagee-Womens Hospital Thomas Jefferson UniversityThomas Jefferson University University of MiamiUniversity of Miami Columbia UniversityColumbia University University of North CarolinaUniversity of North Carolina Case Western Reserve Case Western Reserve

UniversityUniversity George Washington UniversityGeorge Washington University

Wayne State UniversityWayne State University University of ChicagoUniversity of Chicago University of CincinnatiUniversity of Cincinnati University of Texas, University of Texas,

SouthwesternSouthwestern Ohio State UniversityOhio State University University of Texas, San AntonioUniversity of Texas, San Antonio Brown UniversityBrown University University of Texas, HoustonUniversity of Texas, Houston Northwestern UniversityNorthwestern University

Choice of DrugChoice of Drug

17- 17- Hydroxyprogesterone Caproate, Hydroxyprogesterone Caproate, (17P) was chosen because it had been (17P) was chosen because it had been used in previous successful trialsused in previous successful trials

Choice of SubjectsChoice of Subjects

Women who have had a previous Women who have had a previous spontaneous preterm birth are at spontaneous preterm birth are at especially high risk for recurrent preterm especially high risk for recurrent preterm birthbirth

We chose this group of women for We chose this group of women for eligibility to participate in this trialeligibility to participate in this trial

17 P and preterm birth17 P and preterm birthinclusion criteriainclusion criteria::

Documented history of spontaneous Documented history of spontaneous preterm birth at 20preterm birth at 200 0 to 36to 3666 weeks’ gestation weeks’ gestation in a previous pregnancyin a previous pregnancy

Gestational age at entry of 15-20Gestational age at entry of 15-2033 weeks weeks confirmed by ultrasoundconfirmed by ultrasound

Singleton gestation, with no major fetal Singleton gestation, with no major fetal anomaliesanomalies

Exclusion CriteriaExclusion Criteria

Progesterone or heparin treatment Progesterone or heparin treatment during current pregnancyduring current pregnancy

Current or planned cerclageCurrent or planned cerclage Chronic hypertensionChronic hypertension Seizure disorderSeizure disorder Delivery planned outside the CenterDelivery planned outside the Center

Randomization and Follow-upRandomization and Follow-up

If eligible, women were invited to If eligible, women were invited to participate and consented, using a form participate and consented, using a form approved by the Center’s IRBapproved by the Center’s IRB

Given a trial injection of the placebo Given a trial injection of the placebo inert oil, and asked to return in 1 weekinert oil, and asked to return in 1 week

Randomization and Follow-upRandomization and Follow-up

Second visit (at 16Second visit (at 160 0 - 20- 2066 weeks) centrally weeks) centrally randomized using a 2 to 1 ratio to receive randomized using a 2 to 1 ratio to receive injection of 250 mg 17P or a placebo inert injection of 250 mg 17P or a placebo inert oiloil

Then weekly injections of 17P or placebo Then weekly injections of 17P or placebo until delivery or 37 weeksuntil delivery or 37 weeks

Power CalculationsPower Calculations

Primary outcome was delivery <37 weeks’ Primary outcome was delivery <37 weeks’ gestationgestation

Estimated rate of recurrent PTB = 37%Estimated rate of recurrent PTB = 37% 2 to 1 allocation of study drug to placebo2 to 1 allocation of study drug to placebo Sample size = 500 to detect a 33% Sample size = 500 to detect a 33%

reduction in the rate of preterm birthreduction in the rate of preterm birth

Review by Data Monitoring and Safety Review by Data Monitoring and Safety CommitteeCommittee

A scheduled interim analysis was A scheduled interim analysis was performed after 351 subjects had performed after 351 subjects had delivereddelivered

Analysis showed positive effect for the Analysis showed positive effect for the primary outcomeprimary outcome

Enrollment of new subjects was halted Enrollment of new subjects was halted when 463 subjects randomizedwhen 463 subjects randomized

Screening and Screening and RandomizationRandomization

2980 women screened

1941 ineligible 1039 eligible

576 refused consent ordeclined after trial injection

463 randomized

310 17-P 153 placebo

Characteristics of SubjectsCharacteristics of Subjects 17P Placebo17P Placebo

Qualifying deliveryQualifying delivery 30.5 30.5 31.3 wks 31.3 wks Maternal ageMaternal age 26.026.0 26.5 yrs 26.5 yrs MarriedMarried 51%51% 46% 46% African AmericanAfrican American 59%59% 58% 58% Mean BMIMean BMI 26.9 25.926.9 25.9 SmokingSmoking 22%22% 19% 19%

All p > 0.05All p > 0.05

Compliance and Side EffectsCompliance and Side Effects

Compliance with the weekly injections Compliance with the weekly injections was excellentwas excellent

91.5% of the women received their 91.5% of the women received their injections at the scheduled timeinjections at the scheduled time

Side effects were minor and were Side effects were minor and were similar in the 17P and placebo groupssimilar in the 17P and placebo groups

Rates of Births < 37 WeeksRates of Births < 37 Weeks

0%

10%

20%

30%

40%

50%

60%

p = 0.0001

PLACEBO 17 P

54.9%

36.%


0%

5%

10%

15%

20%

25%

30%

35%

P = 0.0165

PLACEBO 17 P

30.7%

20.6%


0%

5%

10%

15%

20%

25%

p = 0.0180

PLACEBO 17 P

19.6%

11.4%

Results by RaceResults by Race

0%

10%

20%

30%

40%

50%

60%

70%

African American p=0.0103 Non African Americanp=0.0044

PLACEBO 17P

52.2%

35.4%

58.7%

37.6%

Rates of Low Birth Weight BirthRates of Low Birth Weight Birth

0%5%

10%15%20%25%30%35%40%45%

BIRTHS <2500 gm p=0.0029 BIRTHS <1500 gm p=0.0834

PLACEBO 17P

41.1%

27.2%

13.9%8.6%

Effectiveness of Treatment Effectiveness of Treatment With 17PWith 17P

5 to 6 Women with a previous 5 to 6 Women with a previous spontaneous preterm birth would need spontaneous preterm birth would need to be treated to prevent one birth <37 to be treated to prevent one birth <37 weeksweeks

12 Women with a previous spontaneous 12 Women with a previous spontaneous preterm birth would need to be treated preterm birth would need to be treated to prevent one birth <32 weeksto prevent one birth <32 weeks

Rates of Neonatal DeathRates of Neonatal Death

0%

1%

2%

3%

4%

5%

6%

7%

p = 0.0805

PLACEBO 17P

5.9%

2.6%

Rates of Neonatal MorbidityRates of Neonatal Morbidity

0%

2%

4%

6%

8%

10%

12%

14%

16%

RDS BPD ROP IVH* NEC*

PLACEBO17P

Percent preterm birth by Percent preterm birth by gestational age of previous preterm gestational age of previous preterm

deliverydelivery

0

10

20

30

40

50

60

70

20-27 weeks' 28-33 weeks' 34-37 weeks'

Placebo17P

Percent preterm birth by number Percent preterm birth by number of previous preterm deliveriesof previous preterm deliveries

0

10

20

30

40

50

60

70

80

One More than One

Placebo17P

Prematurity prevented without Prematurity prevented without evidence of increased infectionevidence of increased infection

ChorioamnionitisChorioamnionitis 1.1 (0.4 – 3.1)1.1 (0.4 – 3.1)

Neonatal sepsisNeonatal sepsis 1.1 (0.3 – 3.6) 1.1 (0.3 – 3.6)

Caveats for 17P cohort Caveats for 17P cohort versus controls:versus controls:

Fewer PTB in prior pregnancies: 1.4 v Fewer PTB in prior pregnancies: 1.4 v 1.6, P=.0071.6, P=.007

When adjusted for variance: Delivery When adjusted for variance: Delivery <37wks RR = 0.7 (0.57, 0.85)<37wks RR = 0.7 (0.57, 0.85)

More stillbirths: 2.0% v 1.3% P=NSMore stillbirths: 2.0% v 1.3% P=NS More miscarriages: 1.6% v 0% P=NSMore miscarriages: 1.6% v 0% P=NS

Odds ratios for outcomes Odds ratios for outcomes comparing previous 17P trials comparing previous 17P trials

with the MFMU resultswith the MFMU results

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Preterm <2500 gm PerinatalDeath

Previous 17P TrialsMFMU Study

Sanchez-Ramos Obstet Gynecol 2005;105:273

Summary of TrialSummary of Trial

The women in this trial encountered very high The women in this trial encountered very high rates of preterm deliveryrates of preterm delivery

The previous preterm delivery was very early, The previous preterm delivery was very early, mean = 30-31 weeks’mean = 30-31 weeks’

One third of the women had had more than One third of the women had had more than one previous preterm deliveryone previous preterm delivery

This rate of preterm birth was similar to other This rate of preterm birth was similar to other observational studies of high risk women in observational studies of high risk women in the MFMU Networkthe MFMU Network

Summary of TrialSummary of Trial 17P treatment was effective in both African 17P treatment was effective in both African

American and Non-African American American and Non-African American womenwomen

17P treatment was effective in preventing 17P treatment was effective in preventing very early as well as later preterm birthsvery early as well as later preterm births

17P Treatment of the women resulted in 17P Treatment of the women resulted in significant reductions in the rates of IVH significant reductions in the rates of IVH and NEC for their infantsand NEC for their infants

Conclusions from TrialConclusions from Trial

Weekly injections of 17- Weekly injections of 17- Hydroxyprogesterone Caproate can Hydroxyprogesterone Caproate can provide significant and powerful provide significant and powerful protection against recurrent preterm protection against recurrent preterm birth and improve the neonatal outcome birth and improve the neonatal outcome for pregnancies at riskfor pregnancies at risk

Decision AnalysisDecision Analysis

Model estimated costs of 17P treatment Model estimated costs of 17P treatment and the costs of preterm birthand the costs of preterm birth

17P treatment was cost effective for 17P treatment was cost effective for women with a prior delivery <32 weekswomen with a prior delivery <32 weeks

17P treatment was also cost effective for 17P treatment was also cost effective for a history of a prior delivery at 32-37 a history of a prior delivery at 32-37 weeksweeks

Odibo AO Obstet Gynecol 2006;108:492

Prophylactic administration of progesterone Prophylactic administration of progesterone by vaginal suppository to reduce the by vaginal suppository to reduce the

incidence of spontaneous preterm birth in incidence of spontaneous preterm birth in women at increased risk: a randomized women at increased risk: a randomized

placebo-controlled trialplacebo-controlled trial

Da Fonseca EB, Bittar RE, Carvalho MHB, Zugaib MDa Fonseca EB, Bittar RE, Carvalho MHB, Zugaib M

Am J Obstet Gynecol 2003;188:419-24Am J Obstet Gynecol 2003;188:419-24

Trial of progesterone suppositoriesTrial of progesterone suppositories

Tertiary medical center in BrazilTertiary medical center in Brazil 144 women, 70% white144 women, 70% white Singleton pregnancies with no symptoms of Singleton pregnancies with no symptoms of

preterm laborpreterm labor Main risk factor was history of a previous preterm Main risk factor was history of a previous preterm

delivery (33 weeks both arms)delivery (33 weeks both arms) Randomized to daily progesterone (100mg) or Randomized to daily progesterone (100mg) or

placebo suppositoriesplacebo suppositories Treated from 24 to 34 weeks’ gestationTreated from 24 to 34 weeks’ gestation

da Fonseca EB Am J Obstet Gynecol 2003;188:419-424

Results of Trial of Progesterone Results of Trial of Progesterone SuppositoriesSuppositories

Placebo ProgesteronePlacebo Progesterone pp

<37 wks<37 wks 28.5%28.5% 13.8%13.8% 0.030.03

<34 wks<34 wks 18.6%18.6% 2.8%2.8%0.0020.002

No information was given about neonatal No information was given about neonatal outcomesoutcomes

Results were not analyzed by intent to treatResults were not analyzed by intent to treat

da Fonseca EB Am J Obstet Gynecol 2003;188:419-424

Conclusions from Progesterone Conclusions from Progesterone Suppository TrialSuppository Trial

The results of this trial show positive The results of this trial show positive results in a population at lower risk for results in a population at lower risk for preterm birth than the MFMU Network preterm birth than the MFMU Network progesterone studyprogesterone study

Suggest a possible alternative method Suggest a possible alternative method of progesterone treatmentof progesterone treatment

Progesterone as a TocolyticProgesterone as a Tocolytic 6 trials have been reported6 trials have been reported Various progesterone compounds usedVarious progesterone compounds used Design of studies variedDesign of studies varied None of the trials found a significant None of the trials found a significant

prolongation of pregnancy with the use of prolongation of pregnancy with the use of the progesterone treatmentthe progesterone treatment

Progesterone treatment of women with Progesterone treatment of women with active uterine contractions should be active uterine contractions should be discouraged outside of research protocolsdiscouraged outside of research protocols

Progesterone Treatment for Progesterone Treatment for Prevention of Preterm BirthPrevention of Preterm Birth

The results of these trials do not represent The results of these trials do not represent the solution to the over-all problem of preterm the solution to the over-all problem of preterm birthbirth

They apply only to women with a previous They apply only to women with a previous spontaneous preterm deliveryspontaneous preterm delivery

Progesterone Treatment for Progesterone Treatment for Prevention of Preterm BirthPrevention of Preterm Birth

These results represent a hopeful beginning: the These results represent a hopeful beginning: the first effective treatments to reduce the risk of first effective treatments to reduce the risk of preterm delivery in women at riskpreterm delivery in women at risk

A major health insurance provider in the U.S. A major health insurance provider in the U.S. has developed a program of treatment with 17P has developed a program of treatment with 17P at a cost of $120 per pregnancyat a cost of $120 per pregnancy

This treatment is cost effective in the prevention This treatment is cost effective in the prevention of preterm deliveryof preterm delivery

Current Problems with 17P Current Problems with 17P TreatmentTreatment

The drug is currently available in the U.S. The drug is currently available in the U.S. only from compounding pharmaciesonly from compounding pharmacies

Some insurance plans, including Medicaid Some insurance plans, including Medicaid do not currently pay for this treatmentdo not currently pay for this treatment

GestivaGestiva

Adeza Biomedical has applied to the FDA Adeza Biomedical has applied to the FDA to produce 17P for the indication of to produce 17P for the indication of prevention of preterm deliveryprevention of preterm delivery

FDA approval should improve FDA approval should improve reimbursement by insurance providers reimbursement by insurance providers including Medicaidincluding Medicaid

Cost of drug will be higherCost of drug will be higher

Further Research QuestionsFurther Research Questions

Mechanism of action of progesterone treatmentMechanism of action of progesterone treatment Comparative efficacy of different progesterone Comparative efficacy of different progesterone

compoundscompounds Effectiveness of progesterone treatment for Effectiveness of progesterone treatment for

women in other risk categorieswomen in other risk categories Multiple gestationMultiple gestation Shortened cervixShortened cervix

Continuing Prematurity Prevention Continuing Prematurity Prevention Trials in the MFMU NetworkTrials in the MFMU Network

Trial of 17P vs. placebo in women with Trial of 17P vs. placebo in women with multiple gestationmultiple gestation

Trial of 17P with Omega-3 fatty acid Trial of 17P with Omega-3 fatty acid supplement vs. 17P and placebo to supplement vs. 17P and placebo to prevent recurrent preterm deliveryprevent recurrent preterm delivery

Trial of 17P vs. placebo in primigravid Trial of 17P vs. placebo in primigravid women with a short cervixwomen with a short cervix

Some Other Current TrialsSome Other Current Trials

17P vs. placebo in twins and triplets 17P vs. placebo in twins and triplets (Obstetrix group)(Obstetrix group)

Progesterone suppositories vs. placebo Progesterone suppositories vs. placebo suppositories in women with a previous suppositories in women with a previous preterm delivery (Columbia Lab sponsored)preterm delivery (Columbia Lab sponsored)

Reducing Rates of PrematurityReducing Rates of Prematurity

Future progress in prevention of preterm Future progress in prevention of preterm delivery is likely to come from primary or delivery is likely to come from primary or secondary prevention strategiessecondary prevention strategies

Once the parturition process has begun, Once the parturition process has begun, attempts to prevent preterm birth are not attempts to prevent preterm birth are not effectiveeffective

Progesterone for the Prevention of Preterm Birth Paul Meis MD.

Documents

preterm delivery progesterone

preterm births

term slide

race slide

spontaneous preterm

progesterone treatment

actions of progesterone

symptoms of preterm