conflict of interest - uab...intrapartum monitoring continuous intrapartum fhr monitoring cesarean...
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Obstetrics on the Cutting Edge: Research Information on the
Progress in OBGYN 2015Progress in OBGYN 2015
Horizon
Alan T. N. Tita, MD, PhDAlan T. N. Tita, MD, PhD
Professor Professor
University of Alabama at BirminghamUniversity of Alabama at Birmingham
Conflict of Interest
●PI for some these studies
Objective● Briefly review research that will likely
influence obstetric practice including:
– Selected UAB / MFMU Network research
– Other recently completed research
NICHD MFMU Network
• Columbia • Case Western• Colorado• Northwestern • Ohio State • Duke • U AlabamaU Alabama• U North Carolina• U Texas‐Houston• U Texas SW‐Dallas• U Utah• U TMB Galveston• Stanford U• Brown U
CESAREAN SECTION OPTIMAL CESAREAN SECTION OPTIMAL ANTIBIOTIC PROPHYLAXISANTIBIOTIC PROPHYLAXIS
(C/SOAP) TRIAL(C/SOAP) TRIAL
HypothesesHypotheses
ExtendedExtended--spectrum prophylaxis spectrum prophylaxis (with (with azithromycinazithromycin)) compared to compared to cefazolincefazolin alone reduces risk ofalone reduces risk ofcefazolincefazolin alone reduces risk of alone reduces risk of
1.1. PostPost--cesarean infectioncesarean infection
2.2. Neonatal morbidityNeonatal morbidity
Antibiotic ProphylaxisAntibiotic Prophylaxis
↓Infectious morbidity: ↓Infectious morbidity: 50%50%
CostCost--effectiveeffective CostCost--effectiveeffective
MugfordMugford: BMJ, 1989: BMJ, 1989SmaillSmaill: Cochrane, 2013: Cochrane, 2013ChelmowChelmow: AJOG, 2004: AJOG, 2004
Unscheduled cesareans: Unscheduled cesareans: Standard preStandard pre--incision incision cefazolincefazolin
FollowFollow--upup Puerperal InfectionPuerperal Infection
Di hDi h 5%5%DischargeDischarge 5%5%
6 weeks PP6 weeks PP 77--12%12%
Extended ProphylaxisExtended Prophylaxis
cefazolincefazolin ++
22ndnd AntibioticAntibiotic22ndnd AntibioticAntibiotic
•• AzithromycinAzithromycin
•• MetronidazolMetronidazol
Why Why AzithromycinAzithromycin??
Covers additional organismsCovers additional organisms
•• UreaplasmaUreaplasma sp. ++sp. ++
•• Most common organisms in Most common organisms in postpost--cesarean infectionscesarean infections
ExtendedExtended--spectrum Prophylaxis:spectrum Prophylaxis:
↓Total infection↓Total infection
↓Hospital stay↓Hospital stay
–– ↓ Costs ↓ Costs
Andrews: Andrews: O&G, 2003O&G, 2003N=597N=597
17%19%
25%28%
15
20
25
30
35
Per
cen
t
Extended
Standard
0.8%
17%
3.6%0
5
10
15
Endometritis Wound Infections Endometritis orWound Infection
P Standard
Tita: Tita: O&GO&G, 2008, 2008
15
20
25
30
met
riti
s (%
)
Narrow spectrum prophylaxis
Routine extended prophylaxis
Trial of extended spectrum prophylaxis
23%
16%
2.1%
0
5
10
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Year
En
do
m
Extended Prophylaxis: Extended Prophylaxis: ConcernsConcerns
GeneralizabilityGeneralizability (1 center)(1 center)
No data on preNo data on pre--incision useincision usepp–– BenefitsBenefits
–– Neonatal exposureNeonatal exposure
CostCost--effectivenesseffectiveness
C/SOAP (N=2000)C/SOAP (N=2000)
NonNon--elective cesareanelective cesarean
RCTRCT
ExclusionsExclusions
RCTRCT(Routine cefazolin for all)(Routine cefazolin for all)
AzithromycinAzithromycin PlaceboPlacebo
C/SOAP TrialC/SOAP Trial
OutcomesOutcomesPostpartum infection (6 weeks)Postpartum infection (6 weeks)
Neonatal/infant morbidity (3 months)Neonatal/infant morbidity (3 months)
StatusStatus
●● N=2013 enrolled (13 sites)N=2013 enrolled (13 sites)
●● Completing followCompleting follow--upup
●● Results within the next yearResults within the next year
Antenatal Late Preterm Steroids Antenatal Late Preterm Steroids (ALPS) RCT(ALPS) RCT
Primary Research Question Primary Research Question --ALPSALPS
●● In patients with an anticipated In patients with an anticipated late late PTBPTB
–– Not previously received a steroids Not previously received a steroids
●● Does antenatal corticosteroids reduce risk ofDoes antenatal corticosteroids reduce risk of●● Does antenatal corticosteroids reduce risk of Does antenatal corticosteroids reduce risk of respiratory and other neonatal morbidity? respiratory and other neonatal morbidity?
Late Preterm Healthcare BurdenLate Preterm Healthcare BurdenDischarge Delays: 42% LP vs. 5% at termDischarge Delays: 42% LP vs. 5% at term
10
2030
40
50
60
Full termLate preterm
Mean difference in the cost of care for a LP infant: $ 3877Mean difference in the cost of care for a LP infant: $ 3877
US projections based on 9.1% LP rate: US projections based on 9.1% LP rate: $1.4 $1.4 billionbillion dollarsdollars
Wang et al, Pediatr 114:372, 2004
0
10
Temp Pro
blems
Hypoglycemia
IV Fl
uids
Resp D
istre
ss
Jaundice
Late preterm
McIntire and Leveno, Obstet Gynecol, 2008;111:35-41
US Late Preterm Singleton US Late Preterm Singleton BirthsBirths
7%
5%
14%
40%<32 weeks32 weeks33 weeks7%
13%
22%
33 weeks34 weeks35 weeks36 weeks
Source: NCHS, final natality dataPrepared by March of Dimes Perinatal Data Center, April 2006.
75% of all pts !
Late preterm infants populate the Late preterm infants populate the NICUNICU
15000
20000
25000
30000
of P
atients
0
5000
10000
15000
23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
Estimated Gestational Age (wks)
Num
ber
o
Clark R et.al, Pediatrix Database, 2005
Neonatal Mortality RatesNeonatal Mortality Rates
*p<0.001, †p=0.02 McIntire D, Leveno K. Obstet Gynecol, 2008;111:37-41
Can we improve outcome of LP Can we improve outcome of LP infants?infants?
Study Design Study Design –– Inclusion Inclusion CriteriaCriteria
●● RCT of BMZ vs. matching placeboRCT of BMZ vs. matching placebo●● Singleton at 34 0/7 to 36 5/7 weeks Singleton at 34 0/7 to 36 5/7 weeks ●● One of 3 categories:One of 3 categories:
–– ROMROM
–– Preterm laborPreterm labor
–– Planned delivery for any indicationPlanned delivery for any indication
●● Likely to deliver >12 hours from 1Likely to deliver >12 hours from 1stst dose dose
1100 Outcome: Outcome: Respiratory Support or Respiratory Support or
Death in 1Death in 1stst 72 hours72 hours●● CPAP or highCPAP or high--flow nasal flow nasal cannulacannula (HHFNC) (HHFNC)
●● Mechanical ventilationMechanical ventilation
●● Oxygen requirement of FiOOxygen requirement of FiO2 2 ≥ 0.3≥ 0.3
●● ECMOECMO
●● Stillbirth or neonatal deathStillbirth or neonatal death
ALPS StatusALPS Status
●● 2792 of planned 2800 enrolled (end 2/2015)2792 of planned 2800 enrolled (end 2/2015)
●● Completing followCompleting follow--up (3 and 6 months)up (3 and 6 months)
●● Expect results within next yearExpect results within next year
CONGENITAL CMV INFECTION PREVENTION
TRIAL(CMV Imm ne glob lin)(CMV Immune globulin)
Research Question
● Does antenatal administration of CMV immune globulin to pregnant women with primary CMV lower the risk of:
1. Congenital CMV infection
2. Infant neurologic morbidity at age 2
CMV●40,000 congenital infections / year
●Primary maternal infection
– 40% fetal transmission40% fetal transmission
● CMV Immune globulin may prevent transmission and reduce sequelae.
– Small observational study
HIG None p-value
CMV Hyperimmune Globulin Therapy
NIGRO, NEJM, 2005
Congenital CMV transmission
16% 40% 0.04
Symptomatic CMV 3.2% 50% <0.001
HIG (N=62)
Placebo (N=61)
P-value
RCT of Hyperimmune globulin
Revello, NEJM, 2014
Congenital CMV 30% 44% 0.13
Adverse obstetric event (PTB, SGA)
13% 2% 0.06
Design
● CMV serology – early (<24 weeks)
● Enroll into trial if positive for 10 CMV
– Sero-conversion
– IgM + low avidity IgG
● Randomization prior to 24 weeks
– CMV Hyperimmune globulin (100m/kg)
– Placebo (identical)
CMV RCT Status
●105,000 screened
●~200 enrolled (N=800)
●Open to all patients
ThyroxineThyroxine Therapy forTherapy forSubclinical Hypothyroidism orSubclinical Hypothyroidism or
HypothyroxinemiaHypothyroxinemia During During PregnancyPregnancy(TSH Trial)(TSH Trial)
Research QuestionIs thyroxine treatment of women withIs thyroxine treatment of women with
a) subclinical hypothyroidism or a) subclinical hypothyroidism or
b) b) hypothyroxinemiahypothyroxinemia
diagnosed in the first half of pregnancydiagnosed in the first half of pregnancydiagnosed in the first half of pregnancy diagnosed in the first half of pregnancy associated with intellectual improvement associated with intellectual improvement in their offspring at age 5 years?in their offspring at age 5 years?
●● Wechsler Preschool and Primary Scale Wechsler Preschool and Primary Scale of Intelligence (WPPSIof Intelligence (WPPSI--III)III)
Subclinical thyroid dysfunction● 3-4% of pregnant women
– Subclinical hypothyroidism: ↑TSH, ↔ FT4
– Hypothyroxinemia: ↔ TSH, ↓FT4
C● Controversy regarding:
– Association with low IQ in offspring
– Ameliorated by treatment during pregnancy
Haddow, NEJM 1999Pop, Clin Endo, 1999, 2003
Design● TFT screen – early (<21 weeks)
● Randomization prior to 21 weeks
– Levothyroxine vs. identical placebo
● 2 strata
– Subclinical hypothyroid (N=670)
– Hypothyroxinemia (N=500)
● 1o outcome: Neurodevelopment at 5 years
TSH RCT Status● 5-year follow-up complete this spring
● Results within 6-12 months
– Universal TFTs during pregnancy?
Automated Automated FetalFetal ECG ECG STSTANANalysisalysis (STAN) as adjunct (STAN) as adjunct
f FHR M it if FHR M it i
STAN TrialSTAN Trial
for FHR Monitoringfor FHR Monitoring(N=11000)(N=11000)
Intrapartum monitoring
Continuous Intrapartum FHR Monitoring
Cesarean delivery rate
%
66% 85% % US women cEFM in labor
%
Trends in CS and CP RatesTrends in CS and CP Rates
15
20
25
0
5
10
1970 1975 1980 1985 1990 1995 2000
Cesarean Section RateCerebral Palsy Rate
Clark SL, et al. Am J Obstet Gynecol 2003;188:628-33.
Sponsored by:NICHDACOGSMFM
Category II: IndeterminateCategory II: Indeterminate
●● All tracings not categorized as Category All tracings not categorized as Category I or III I or III
●● Appreciable fraction Appreciable fraction -- 33%33%
●● Management uncertainManagement uncertainE amples●● Management uncertainManagement uncertain
• Moderate variability with bradycardia• Minimal FHR variability• Absent variability with no recurrent decels• Recurrent variable decels with moderate variability• Recurrent late decels with moderate variability
Examples
A Cat II tracing A Cat II tracing needsneeds a back up test! a back up test!
●● Fetal scalp pH: < 3% of institutions in the U.S. Fetal scalp pH: < 3% of institutions in the U.S. (ACOG Survey of U.S. Hospitals)(ACOG Survey of U.S. Hospitals)
●● Others have never been proven or accepted: Others have never been proven or accepted: Continuous scalp pH, fetal pulse Continuous scalp pH, fetal pulse oximetryoximetry
●● ST AnalysisST Analysis–– developed for this purpose in minddeveloped for this purpose in mind
–– tested in these labor situationstested in these labor situations
–– the only currently FDA approved backupthe only currently FDA approved backup
Device Description Device Description (NEOVENTA)(NEOVENTA)
●● Std EFM capabilities:Std EFM capabilities:–– External ultrasound or fetal External ultrasound or fetal
spiral electrode (FSE)spiral electrode (FSE)
–– TOCO or IUPC TOCO or IUPC
& &
●● Fetal ECG (ST) AnalysisFetal ECG (ST) Analysis
Basis for STAN TechnologyBasis for STAN Technology
“Labor puts the fetus on a treadmill”
What is being recorded?What is being recorded?
30 ECG complexes
T-wave amplitude is divided by
the QRS amplitude which gives T/QRS ratio
average ECG
STAN clinical managementSTAN clinical management
Examples of STAN Tracings: Category II Examples of STAN Tracings: Category II FHRFHR
Second stage recording NVD, Apgar 9-10 CA pH 7.18 CV pH 7.27
CS FD, Apgar 8-9 CA pH 7.14, Bdecf 8.7 mmol/L CV pH 7.34, Bdecf 6.3mmol/L
STAN clinical experienceSTAN clinical experience
Cochrane ReviewCochrane ReviewNeonatal EncephalopathyNeonatal Encephalopathy
Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring during labour. during labour. Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews 2006, 2006,
Issue 3. Art. No.: CD000116. DOI: Issue 3. Art. No.: CD000116. DOI: 10.1002/14651858.CD000116.pub2.10.1002/14651858.CD000116.pub2.
Cochrane ReviewCochrane ReviewCord pH < 7.05 + Base Deficit > 12 mmol/LCord pH < 7.05 + Base Deficit > 12 mmol/L
Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring during labour. during labour. Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews 2006, 2006,
Issue 3. Art. No.: CD000116. DOI: Issue 3. Art. No.: CD000116. DOI: 10.1002/14651858.CD000116.pub2.10.1002/14651858.CD000116.pub2.
Cochrane ReviewCochrane ReviewOperative Vaginal DeliveryOperative Vaginal Delivery
Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring during labour. during labour. Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews 2006, 2006,
Issue 3. Art. No.: CD000116. DOI: Issue 3. Art. No.: CD000116. DOI: 10.1002/14651858.CD000116.pub2.10.1002/14651858.CD000116.pub2.
Cochrane ReviewCochrane ReviewCesarean DeliveryCesarean Delivery
Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring Neilson JP. Fetal electrocardiogram (ECG) for fetal monitoring during labour. during labour. Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews 2006, 2006,
Issue 3. Art. No.: CD000116. DOI: Issue 3. Art. No.: CD000116. DOI: 10.1002/14651858.CD000116.pub2.10.1002/14651858.CD000116.pub2.
A study in US?A study in US?
●● No RCT in North AmericaNo RCT in North America●● Differences in practice patternsDifferences in practice patterns
F t l H liF t l H li–– Fetal pH samplingFetal pH sampling–– Operative deliveriesOperative deliveries–– Intermittent EFMIntermittent EFM
●● Differences in populationDifferences in population
Study Design Study Design -- STANSTAN
RCT: 2 groupsRCT: 2 groups
1. Fetal STAN electrode inserted and data available 1. Fetal STAN electrode inserted and data available to caregivers (open group)to caregivers (open group)
2. Fetal STAN electrode inserted, but data masked 2. Fetal STAN electrode inserted, but data masked to the caregivers (masked group)to the caregivers (masked group)
Primary OutcomePrimary Outcome
●● Any of the following:Any of the following:–– intrapartum fetal deathintrapartum fetal death
–– neonatal deathneonatal deathneonatal deathneonatal death
–– Apgar score ≤ 3 at 5 minutesApgar score ≤ 3 at 5 minutes
–– seizure(s)seizure(s)
–– cord artery pH ≤ 7.05 and BD cord artery pH ≤ 7.05 and BD >> 1212
–– neonatal encephalopathyneonatal encephalopathy
–– Intubation for ventilation at deliveryIntubation for ventilation at delivery
ResultsResults
●● N=11,108N=11,108Outcome Open STAN Masked STAN P-value
1o outcome 1.4% 1.3% 0.43
Cesarean 17% 16% 0.29
Operative VD 6.0% 6.0% 0.79
Effect of Expanded Effect of Expanded Midwifery and Hospitalist Midwifery and Hospitalist
Services on PrimaryServices on PrimaryServices on Primary Services on Primary Cesarean RatesCesarean Rates
Rosenstein, SMFM 2015
ObjectiveObjective
●● Impact of changing L&D care from: Impact of changing L&D care from: –– a private practice model (individual a private practice model (individual ObsObs))
–– to 24to 24--hr Obstetricianhr Obstetrician--midwife hospitalistmidwife hospitalistto 24to 24 hr Obstetricianhr Obstetrician midwife hospitalist midwife hospitalist model model
DesignDesign
●● Prospective (2005Prospective (2005--2014)2014)
●● Before and after designBefore and after design
●● SingletonsSingletons●● SingletonsSingletons
●● Single community hospitalSingle community hospital
ResultsResults
Outcome Before After p-value
Cesarean 32% 25% 0.007
VBAC 11% 23% 0.001
*Rates unchanged in publicly insured service with prior hospitalist model
PRESERVEPRESERVE--1 RCT1 RCT
GoalGoal
●● Test Test antithrombinantithrombin (recombinant) (recombinant) replacement for the treatment of replacement for the treatment of early onset preeclampsiaearly onset preeclampsia
PRESERVEPRESERVE--1 Rationale1 RationaleAntithrombinAntithrombin
●● Anticoagulant and antiAnticoagulant and anti--inflammatoryinflammatory
●● Deficient in preeclampsiaDeficient in preeclampsia
●● Promising preliminary studiesPromising preliminary studies●● Promising preliminary studiesPromising preliminary studies–– Pregnancy prolongation (1 week)Pregnancy prolongation (1 week)
–– Higher birth weightHigher birth weight
–– Lower SGA riskLower SGA risk
PRESERVEPRESERVE--1 Design1 Design
●● RCTRCT–– AntithrombinAntithrombin infusioninfusion
–– PlaceboPlacebo
●● Inclusion criteriaInclusion criteria–– Early onset preeclampsia Early onset preeclampsia
–– 23 0/7 to 29 6/7 weeks23 0/7 to 29 6/7 weeks
–– Expectant management plannedExpectant management planned
●● Outcomes: GA and Neonatal morbidityOutcomes: GA and Neonatal morbidity