vaginal progesterone for prevention of preterm labor in

7/21/2019 Vaginal Progesterone for Prevention of Preterm Labor In

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Vaginal progesterone forprevention of preterm labor in

asymptomatic twin pregnancies

with sonographic short cervix: arandomized clinical trial of ecacy

and safety

Disusun Oleh :



ABSTRAT



!"R!#S$

Progesteron Therapy

Therapy forreduction of

preterm labor

Inasymptomatic

women withtwin

pregnancies

Sonographicshort

cervix

Main Purpose: Toevaluate the value



%$T&#'S

andomi!ed controlled study wasconducted in Mansoura "niversity#ospital and privatepracticesettings in Mansoura$%gypt&

The primary outcome measurewas preterm labor before '(wee)s of gestation

The secondary outcomemeasures were neonatalrespiratory distress syndrome*DS+ and early neonatal death*%,D+

'-- women with

dichorionic twin pregnancy

-./ asymptomatic women

with cervical length of -/0-. mm at -/0-( wee)s of

gestation

The study group

*n 1 2-.+ received

vaginal progesteronesuppositories in a

dose of (// mg daily

The control group *n1 2-.+ received no

treatment



R$S"(TS

--( women

223 in studygroup

2/4 incontrolgroup

5inal analysis

St)dy*ro)p

Theduration of pregnancy wassigni6cantly longer

The incidence of preterm laborbefore '( and '- wee)s ofgestation was signi6cantlylower

The neonatal morbidities and mortality weresigni6cantly ower in the study group as shown bylower incidence of very low * 72.// gm+ birthweight$ neonatal DS$ the need for mechanicalventilation and %,D&



#+("S,#+

8aginal progesterone administration in asymptomatic twinpregnancies with sonographic short cervix *-/0-. mm+ at -/0-(wee)s of gestation is e9ective and safe treatment for reducingthe incidence of preterm labor with subseuent reduction in the

neonatal morbidities and mortality associated with pretermbirth&



,+TR#'"T,#+



Pretermbirth

Delivery before ';wee)s of

gestation

In -//.$ about ;&3 < of

all live births in %nglandand =ales were preterm

Spontaneo)s pretermlabor

Occurs more freuently intwins compared withsingletons> however$ theneonatal outcome isgenerally the same atsimilar gestational ages

One of the most dependablepredictors of preterm labor inboth singleton and twingestations is a sonographicshort cervix& ?lthough themean cervical length in twinpregnancies is similar to that ofsingleton pregnancies *'4 mm+$the same cervical lengthconfers higher ris) for pretermlabor in twin than in singletonpregnancies&



In pregnant women with short cervix

Prophylactic progesteronetherapy$ cervical cerclageand insertion of cervical

pessaries&

&ave been

shown to bee-ective

8aginal progesteroneadministration was associated with lowrecurrence rate ofpreterm birth

8aginal progesterone administration was associated withdelayed cervical shortening as pregnancy progressed$ andlower freuency of admission to the neonatal intensive care

unit*,I@"+

Preterm labor was reduced by (( <> however$ this reductionwas not associated with signi6cant improvement in theneonatal outcome

(. < reduction in the rate of preterm labor before '' wee)sof gestation with improvement in neonatal outcome

In the lac) of suAcient clinicaltrials considering cervical

length when evaluating thee9ect of vaginal progesteronefor prevention of preterm labor

in twin pregnancies$

=e aimed in this study toassess the value of starting

vaginal progesterone therapyat -/0-( wee)s of gestation

for reduction of pretermlabor in asymptomatic twin

pregnancies withsonographic short cervix *-/0

-. mm+&



%AT$R,A( A+'%$T&#'S



This was a prospective$ randomi!ed$ controlled$ parallelgroup studyconducted during the period from Bune -/2- through ,ovember -/2( inMansoura "niversity #ospital and private practice settings in Mansoura$ %gypt

=omen aged -/0'. years old with dichorionic twin pregnancy were selectedfor measurement of cervical length by transvaginal sonography *T8S+ at -/0

-( wee)s of gestation&

Inclusion criteria : those who had cervical length of -/0-. mm with nosymptoms or signs of impending preterm labor&

• *2+ )nown allergy or contraindication*relative or absolute+ to progesteronetherapy

• *-+monochorionic twins• *'+ )nown maCor fetal structural or

chromosomal abnormality• *(+ single fetal demise

• *.+ 5etal reduction in current pregnancy• *3+ cervical cerclage in current pregnancy• *;+ medical conditions that may lead to

preterm labor• *4+ rupture of membranes• *+ 8aginal bleeding&

%xclusio

ncriteria



*ro)p of $xperiment S)b.ect

?ll womenparticipating in the

study wererandomly

into two groups*2:2+

8aginalprogesterone group

*study group+

,o treatmentgroup *control

group+

eceived vaginal progesteronesuppositories in a dose of (// mg

dailystarting at -/0-( wee)s of gestation

till '; wee)s of gestation

2& ?ll women were followed every -wee)s$ women were interviewed todetermine the occurrence of adverseevents or signs of preterm labor andcompliance with medication wasassessed

-& =omen who developed preterm

labor were managed byhospitali!ation$ administration oftocolytics$ corticosteroids andantibiotics *in cases with PPOM+ andobservation until delivery

'& The primary outcome measure of thisstudy was preterm labor before '(

wee)s of gestation(& The secondary outcome measureswere the neonatal DS and earlyneonatal death *%,D+

2& ?ll women were followed every -wee)s$ women were interviewed todetermine the occurrence of adverseevents or signs of preterm labor andcompliance with medication wasassessed

-& =omen who developed preterm

labor were managed byhospitali!ation$ administration oftocolytics$ corticosteroids andantibiotics *in cases with PPOM+ andobservation until delivery

'& The primary outcome measure of thisstudy was preterm labor before '(

wee)s of gestation(& The secondary outcome measureswere the neonatal DS and earlyneonatal death *%,D+



STAT,ST,A( A+A(/S,S

2& The statistical analysis was performed using the IEM SPSS Statistics$ version -/&/ for=indows&

-& @ontinuous variables were expressed as mean F standard deviation *SD+ and categoricalvariables were expressed as freuencies and percentages&

'& The normality distribution of continuous variables was tested with the Golmogorov0Smirnov and Shapiro0=il) tests&

(& Di9erences among continuous variables with normal distribution were compared with the ttest$ while for continuous variables without normal distribution$ nonHparametric tests wereused and di9erences were compared with the Mann0=hitney " test

.& Di9erences between percentages were compared with the 5ishers exact test

3&The relati ve ris) *+ and odds ratio *O+ were used to compare the li)elihood of an eventoccurring between two groups



R$S"(TS



The perinatalproblems thatinterfered with

continuation of theintervention

PregnancyHinduced

hypertension *PI#+

?cute fatty liver

of pregnancy

?ntepartumhemorrhage*?P#+ due to

placenta previa

Preterm prematurerupture of

membranes *PPOM+

Discordant

fetal growth

Single fetaldemise and

I"5D

In ' women in thestudy group

and 3 women inthe control group&



,ote :• The duration of pregnancy *gestational age at delivery+ was signi6cantly longer in the

study group than in the control group• The incidence of preterm labor before '( wee)s of gestation was signi6cantly lower in

the study group than in the control group•

The incidence of preterm labor before '- wee)s of gestation was signi6cantly lower inthe study group than in the control group

• The neonatal morbidities and mortality associated with preterm labor weresigni6cantly lower in the study group than in the control group as shown by lowerincidence of very low * 72.// gm+ birth weight$ lower incidence of neonatal DS$lower incidence of the need for mechanical ventilation and lower incidence of %,D



',S"SS,#+



Preterm labor The main cause of neonatal morbidityand mortality in twin pregnancies

@auseby DS

@ause byprematurity

Decrease in the progesterone which is )nown to have an importantrole in maintaining the uterine uiescence in the latter half ofpregnancy through limitation of the production of stimulatoryprostaglandins and inhibition of the expression of oxytocin andprostaglandin receptors and gap Cunctions within the myometrium

On 5ebruary -/22$ the "nited States *"S+ 5ood and Drug ?dministration*5D?+ approved the administration of progesterone supplementation *2;Hhydroxyprogesterone caproate+ during pregnancy to decrease the ris) ofrecurrent preterm labor in women with a history of at least one previousspontaneous preterm labor&



In Our Study :

• ?dministration of vaginal progesterone from the midtrimester inasymptomatic twin pregnancies with short cervix *-/0-. mm+was associated with nearly '' < relative reduction in the rate ofpreterm labor before '( wee)s gestation

• =e found improvement in the neonatal outcome specially thereduction in the rate of delivery of neonates with very low birthweight * 72.// gm+ who are at great ris) of development ofneonatal morbidities

• 8aginal progesterone reduced the rate of preterm birth *de6nedas 7'( or 7'' wee)s+ by ((0(. < when given to women withshort cervix in the midtrimester&

• =e found that neonatal DS was signi6cantly lower in womenwho received vaginal progesterone and this was due to thesigni6cant increase in the duration of pregnancy and thedecrease in the rate of preterm labor before '( wee)s of

gestation&



On the other hand$ our results contradict the results of the previousrandomi!ed controlled trial because :

• In these studies$ women with twin pregnancy were healthy and have no)nown ris)s for preterm labor apart from having twin pregnancy while in ourstudy$ women with twin pregnancy had short cervix which is a reliablepredictor for preterm labor&

• =e used higher doses of vaginal progesterone *(// mg once daily+ whichmay have higher e9ects for prevention of preterm labor&

=e used reduction of preterm labor before '( wee)s as the primary outcomemeasure because cervical length 7-. mm in women with twin pregnancy at -/0-( wee)s of gestation carries a ./ < ris) of preterm labor before '- wee)s

=e used -/ mm cervical length as a lower limit because a systematic reviewand metaHanalysis showed that cervical length 7-/ mm at -/0-( wee)s ofgestation in women with twin pregnancy was a maCor predictor of preterm birth

before '( and '- wee)s of gestation



STR$+*T& and (,%,TAT,#+ of #"RST"'/

Strength

• It was a randomi!ed controlledthough blinding was not possiblebecause no intervention was used inthe control group&

• ?ll women in whom outcomesmeasures were available wereincluded in the 6nal analysis$irrespective of whether they

continued or discontinued theintervention&• Minimi!ation of the heterogeneity

that present in the population oftwin pregnancies by exclusion ofmonochorionic twin gestations&

Jimitation

• It was not done as a placeboHcontrolled trial with lac) of blinding*ris) of bias+

• Performing the allocationconcealment by sealed$ opaueenvelopes$ which is not therecommended method&

• The study was conducted on a

relatively small cohort with highdropped out rate *2/&( <+&



#+("S,#+

8aginal progesterone administration to asymptomatic womenwith twin pregnancy and sonographic short cervix *-/0-. mm+in the midtrimester *-/0-( wee)s of gestation+ is e9ective andsafe treatment for reducing the incidence of preterm labor withsubseuent reduction in the neonatal morbidities and mortalityassociated with preterm birth&



T&A+0 /#"

vaginal progesterone for prevention of preterm labor in

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