3/3/2012 1 Preterm Birth Preterm Birth Kym Kym Gohn Gohn, DO , DO Preterm Birth Preterm Birth Leading cause of neonatal mortality in Leading cause of neonatal mortality in US US Accounts for 35% of all U.S. healthcare Accounts for 35% of all U.S. healthcare spending for infants spending for infants Accounts for 10% U.S. healthcare Accounts for 10% U.S. healthcare spending for all children spending for all children
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Preterm BirthPreterm Labor Interventions Non-pharmacologic therapy of no proven benefit Bed rest, hydration, pelvic rest Tocolytic therapy may, at best, transiently delay delivery
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3/3/2012
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Preterm BirthPreterm Birth
Kym Kym GohnGohn, DO, DO
Preterm BirthPreterm Birth
Leading cause of neonatal mortality in Leading cause of neonatal mortality in
USUS
Accounts for 35% of all U.S. healthcare Accounts for 35% of all U.S. healthcare
spending for infantsspending for infants
Accounts for 10% U.S. healthcare Accounts for 10% U.S. healthcare
spending for all childrenspending for all children
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Preterm BirthPreterm Birth
More than 500,000 live preterm births More than 500,000 live preterm births
annuallyannually
Births <37weeks and >20 weeksBirths <37weeks and >20 weeks
Responsible for 75% of neonatal Responsible for 75% of neonatal
mortalitymortality
Preterm births <32 weeks account for 1Preterm births <32 weeks account for 1--
rate has remained unchanged over the last 40 rate has remained unchanged over the last 40
yearsyears
Most preventative and therapeutic efforts are Most preventative and therapeutic efforts are
ineffectiveineffective
Preterm birth remains the single largest Preterm birth remains the single largest
challenge for obstetricians todaychallenge for obstetricians today
Importance of corticosteroids, GBS prophylaxis, Importance of corticosteroids, GBS prophylaxis,
atraumatic delivery, availability of NICUatraumatic delivery, availability of NICU
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Preterm BirthPreterm Birth
Neonatal mortality rates have decreased in recent Neonatal mortality rates have decreased in recent yearsyears 2020--30% survival at 2230% survival at 22--23 weeks23 weeks
50% survival at 2450% survival at 24--25 weeks25 weeks
90% survival at 2890% survival at 28--29 weeks29 weeks
Short term morbiditiesShort term morbidities RDS, IVH, PVL, NEC, BPD, sepsis, PDARDS, IVH, PVL, NEC, BPD, sepsis, PDA
Long term morbiditiesLong term morbidities Cerebral palsy, mental retardationCerebral palsy, mental retardation
Risk directly related to gestational age Risk directly related to gestational age
CP risk 2/1000 live births overallCP risk 2/1000 live births overall
placebo controlled trial in NEJM 2003placebo controlled trial in NEJM 2003
Women between 16Women between 16--20 weeks with 20 weeks with
history of prior preterm birthhistory of prior preterm birth
Patients received 250mg 17P weekly Patients received 250mg 17P weekly
until 36 weeksuntil 36 weeks
Preterm Labor Therapy: Preterm Labor Therapy:
17P17P
Patients had significantly reduced risk of Patients had significantly reduced risk of
preterm birth at <37, <35 and <32 weekspreterm birth at <37, <35 and <32 weeks
Neonatal outcomes also significantly Neonatal outcomes also significantly
improved with reduced risk of NEC, IVH improved with reduced risk of NEC, IVH
and oxygen therapy durationand oxygen therapy duration
Risk of preterm birth still ranged from 11Risk of preterm birth still ranged from 11--
36%36%
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ProgesteroneProgesterone
Literature review 2000Literature review 2000--20082008
History of prior spontaneous preterm birthHistory of prior spontaneous preterm birth Weekly IM 17P initiated at 16Weekly IM 17P initiated at 16--20 weeks or 100mg vaginal 20 weeks or 100mg vaginal
TwinsTwins--not indicated unless history of prior SPTBnot indicated unless history of prior SPTB--250mg IM injection 17P weekly or CL <15mm, 200mg 250mg IM injection 17P weekly or CL <15mm, 200mg vaginal suppository dailyvaginal suppository daily
Arrested preterm laborArrested preterm labor 400mg daily vaginal suppository or 341mg IM twice weekly400mg daily vaginal suppository or 341mg IM twice weekly
Tocolytic TherapyTocolytic Therapy--
RitodrineRitodrine
Only medication approved by FDA for Only medication approved by FDA for treatment of preterm labortreatment of preterm labor
Due to maternal/fetal complications: cost and Due to maternal/fetal complications: cost and limited evidence of improved outcomes, limited evidence of improved outcomes, ritodrine currently not widely usedritodrine currently not widely used
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Tocolytic Therapy: Tocolytic Therapy:
TerbutalineTerbutaline
Most commonly used beta mimeticMost commonly used beta mimetic
Administered via oral, IV or Administered via oral, IV or subcutaneous routessubcutaneous routes
Like ritodrine, delays delivery but has not Like ritodrine, delays delivery but has not been demonstrated to reduce rate of been demonstrated to reduce rate of preterm birthpreterm birth
Subcutaneous terbutaline pump has not Subcutaneous terbutaline pump has not been shown to be effectivebeen shown to be effective
Tocolytic Therapy: Tocolytic Therapy:
Magnesium SulfateMagnesium Sulfate
First described as tocolytic 1977First described as tocolytic 1977
Initial bolus 4Initial bolus 4--6 grams over 30 minutes6 grams over 30 minutes Maintenance infusion 1Maintenance infusion 1--3 grams/hour3 grams/hour
Common SE: nausea, flushing, lethargy, Common SE: nausea, flushing, lethargy, blurred visionblurred vision
Deep tendon reflexes lost >12mg/dLDeep tendon reflexes lost >12mg/dL Respiratory depression >14mg/dLRespiratory depression >14mg/dL
Cardiac arrest >18mg/dLCardiac arrest >18mg/dL
Reversal with 1 gram calcium gluconateReversal with 1 gram calcium gluconate
Followed by total 24 hour dose <200mgFollowed by total 24 hour dose <200mg
Duration of therapy 24Duration of therapy 24--48 hours48 hours
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Tocolytic TherapyTocolytic Therapy--
IndomethacinIndomethacin
Potential severe fetal effectsPotential severe fetal effects
Decreased urine outputDecreased urine output
OligohydramniosOligohydramnios
Constriction of ductus arteriosusConstriction of ductus arteriosus
Due to risks of long term therapyDue to risks of long term therapy
Limit duration to <48 hoursLimit duration to <48 hours
Limit use to <30Limit use to <30--32 weeks32 weeks
Often employed as second line agentOften employed as second line agent
Tocolytic Therapy: Tocolytic Therapy:
Calcium Channel BlockersCalcium Channel Blockers
Nifedipine most widely studiedNifedipine most widely studied
Similar efficacy to other agentsSimilar efficacy to other agents
Loading dose of 20mg orallyLoading dose of 20mg orally Followed with 10Followed with 10--20 mg q 620 mg q 6--8 hours8 hours
Sublingual route hazardousSublingual route hazardous Risk of acute/severe hypotensionRisk of acute/severe hypotension
Recent systematic review and metaanalysisRecent systematic review and metaanalysis Significant reduction in PTD within 7 days vs. B agonistsSignificant reduction in PTD within 7 days vs. B agonists
No difference efficacy/adverse outcomes vs. Magnesium No difference efficacy/adverse outcomes vs. Magnesium sulfatesulfate
Fewer maternal SE vs. Mag sulfate and B agonistsFewer maternal SE vs. Mag sulfate and B agonists
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Tocolytic TherapyTocolytic Therapy--Other Other
AgentsAgents
Oxytocin antagonistsOxytocin antagonists
Atosiban not available in U.S.Atosiban not available in U.S.
May delay delivery 24May delay delivery 24--48 hours48 hours
“The utility of antibiotics to prolong pregnancy “The utility of antibiotics to prolong pregnancy
and reduce neonatal mortality in women with and reduce neonatal mortality in women with
preterm labor and intact membranes has been preterm labor and intact membranes has been
evaluated in numerous randomized clinical evaluated in numerous randomized clinical
trials. Antibiotic use intended only for trials. Antibiotic use intended only for
pregnancy prolongation in women with preterm pregnancy prolongation in women with preterm
labor with intact membranes does not have labor with intact membranes does not have
shortshort--term neonatal benefits and may be term neonatal benefits and may be
associated with longassociated with long--term harm.”term harm.”
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Corticosteroid TherapyCorticosteroid Therapy
Single most effective intervention to Single most effective intervention to
improve neonatal outcomeimprove neonatal outcome
Administered between 24Administered between 24--34 weeks34 weeks
Repetitive dosing not indicatedRepetitive dosing not indicated
First line agent: betamethasoneFirst line agent: betamethasone
Alternative agent: dexamethasoneAlternative agent: dexamethasone
May be less effective reducing IVH/PVLMay be less effective reducing IVH/PVL
Corticosteroid Therapy Corticosteroid Therapy
Rescue CourseRescue Course--ACOG 2011ACOG 2011
A single rescue course of antenatal A single rescue course of antenatal corticosteroids may be considered if the corticosteroids may be considered if the antecedent treatment was given more than 2 antecedent treatment was given more than 2 weeks prior, the gestational age is less than 32 weeks prior, the gestational age is less than 32 6/7 weeks, and the women are judged by the 6/7 weeks, and the women are judged by the clinician to be likely to give birth within the next clinician to be likely to give birth within the next week. However, regularly scheduled repeat week. However, regularly scheduled repeat courses or multiple courses (more than 2) are courses or multiple courses (more than 2) are not recommended. Further research regarding not recommended. Further research regarding the risks and benefits, optimal dose, and timing the risks and benefits, optimal dose, and timing of a single rescue course of steroid treatment of a single rescue course of steroid treatment is needed.is needed.
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Preterm Birth: Delivery Preterm Birth: Delivery
IssuesIssues
Virtually all preterm breech birth infants Virtually all preterm breech birth infants
delivered via cesarean sectiondelivered via cesarean section
Cerclage may benefit some patients by Cerclage may benefit some patients by preventing membrane prolapse and bacterial preventing membrane prolapse and bacterial infectioninfection
Process starts before 20 weeks in many Process starts before 20 weeks in many womenwomen
Reduced risk RDS, NEC, and PDAReduced risk RDS, NEC, and PDA
Intrapartum GBS prophylaxis indicated regardless of Intrapartum GBS prophylaxis indicated regardless of prior antibiotic therapyprior antibiotic therapy
Oral erythromycin/extended spectrum ampicillinOral erythromycin/extended spectrum ampicillin--clavulanic acid not beneficialclavulanic acid not beneficial
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Expectant Management Expectant Management
Preterm PROMPreterm PROM
After viability, safety of expectant After viability, safety of expectant management at home not establishedmanagement at home not established
No controlled studies have found No controlled studies have found cerclage retention after PROM to cerclage retention after PROM to improve outcomeimprove outcome
With active HSV, expectant management With active HSV, expectant management with antiviral therapy may be preferablewith antiviral therapy may be preferable
Need to balance against risk of prematurityNeed to balance against risk of prematurity
Expectant Management Expectant Management
Preterm PROM before Preterm PROM before
ViabilityViability
No evidence based guidelinesNo evidence based guidelines
Initial period of inpatient monitoringInitial period of inpatient monitoring
Bedrest/pelvic rest possibly aid resealingBedrest/pelvic rest possibly aid resealing
Early identification of infection or abruptionEarly identification of infection or abruption
Monitor temperatures at homeMonitor temperatures at home
Readmit to hospital at viabilityReadmit to hospital at viability
Expectant management with corticosteroidsExpectant management with corticosteroids