Preterm Birth Yinka Oyelese, MD, MRCOG Associate Professor, Maternal Fetal Medicine UTHSC
Preterm birth rates in the United States < 37 weeks 12.9% %
Preterm birth in the US One preterm birth every minute!
To put it in perspective….. <ul><li>One preterm birth each minute </li></ul><ul><li>60 preterm births by the time this tal...
Preterm birth <ul><li>75-80% of all perinatal mortality </li></ul><ul><li>50% of all long term neurodevelopmental morbidit...
<ul><li>Infants born preterm are at increased risk of: </li></ul><ul><li>Respiratory Distress syndrome </li></ul><ul><li>C...
50% of long term major morbidity among non-anomalous fetuses: <ul><li>Cerebral palsy </li></ul><ul><li>Mental retardation ...
 
Costs affect insurance rates, taxes, and PAY CHECKS!
Sources of preterm birth, United States 2000 Ananth et al, Obstet Gynecol, 2006 Overall (%) Singletons (%) Twins (%) Spont...
Preterm births in the United States
Spontaneous PTB Medically indicated PTB Preterm PROM
SPB Source of Preterm Birth Tucker et al. Obstet Gynecol 1991 Spontaneous 30-50% Preterm PROM 30-40% Indicated 20-30%
Medically indicated Spontaneous Overall SROM
Preterm Birth Changes between 1989-00, US Whites Blacks All PTB 14% 15% Spont PTB 3% 27% Med-ind 55% 32% PNM 30% 25%
Preterm Birth Trends Whites (%) Blacks (%) 89 00 Δ % 89 00 Δ % Total PTB 8.3 9.4 14 18.5 16.2 -15 pPROM 1.1 0.8 -23 2.3 ...
Indicated Preterm Birth Tucker et al. 1991 Meis et al. 1986 Singletons Twins Preeclampsia 43% 44% FGR/fet dist 37% 33% Ab...
Ananth and Vintzileos AJOG 2006 Ischemic Placental Disease Among… Ischemic placental disease present in Term births 1 in 1...
 
Etiologies Stress Infection Bleeding Uterine overdistension
<ul><li>Preterm birth is a “syndrome” </li></ul><ul><li>Inflammation/Infection (~40%) </li></ul><ul><li>Maternal/fetal str...
Some pathways through which preterm birth may occur
Some pathways through which preterm birth may occur
Risk factors <ul><li>Prior preterm birth </li></ul><ul><li>Poor socio-economic status </li></ul><ul><li>Black race </li></...
Preterm babies are more likely to have preterm births as adults Porter et al. Obstet Gynecol 1997;90:63-67 <ul><li>1405...
Maternal and Paternal Influences <ul><li>77,452 boys and girls in Norway who later became parents </li></ul><ul><li>Gestat...
Recurrence of preterm birth
Recurrence of preterm birth
 
Average length of gestation by plurality
<ul><li>Over 80% of patients who present with regular painful contractions go on to deliver at term </li></ul><ul><li>Most...
More than 1/2 of patients who deliver preterm have no risk factors More than 2/3 of patients with traditional risk factors...
Fetal fibronectin
 
Fetal fibronectin
 
 
 
 
Cervical Length as Predictor of SPB <ul><li>The risk of SPB is increased in women with short cervix. Abnormal cervical len...
 
 
 
Transvaginal sonographic cervical assessment
Interventions that have been used <ul><li>Bed rest </li></ul><ul><li>Intravenous hydration </li></ul>
Are there any therapeutic interventions to prevent SPTB?
Types of Cervical Cerclage <ul><li>History-indicated </li></ul><ul><li>Physical exam-indicated </li></ul><ul><li>Ultrasoun...
The Use of Cervical Cerclage for a Short Cervix ( Ultrasound-Indicated Cerclage ) 4 RCT’s <ul><li>Rust-2000 Unselecte...
Multicenter RCT on the Use of Cervical Cerclage in High Risk Pregnancies (Report of the MRC/RCOB, Br J Obstet Gynaecol 19...
Cerclage for dilated cervix with membranes at or beyond the external os Althusius et al, Am J Obstet Gynecol 2003 Cerclage...
Management of Cervical Insufficiency and Bulging Fetal Membranes (at 18-26 weeks) (Daskalakis et al Obstet Gynecol 2006;10...
Use of Cerclage for Prevention of SPB in Women With Prior SPB. A Meta-analysis of 4 RCTs (Berghella V, Odibo A, To M, Rus...
Multicenter Randomized Trial of Cerclage For Preterm Birth Prevention In High-Risk Women With Shortened Mid-Trimester Ce...
Tocolytics <ul><li> -adrenergic agents </li></ul><ul><li>Magnesium sulfate </li></ul><ul><li>Prostaglandin synthetase inh...
Magnesium sulfate! Good or evil?
Contraindications to Tocolysis <ul><li>Conditions where delivery is indicated such as </li></ul><ul><li>Severe preeclampsi...
Goals of tocolysis <ul><li>To allow steroid administration </li></ul><ul><li>To allow transport or to facilitate delivery ...
Calcium channel blockers <ul><li>Inhibit calcium entry into cells </li></ul><ul><li>Nifedipine most commonly used </li></...
Calcium channel blockers <ul><li>Side effects: </li></ul><ul><li>Hypotension </li></ul><ul><li>Headaches </li></ul><ul><li...
Cyclooxgenase inhibitors <ul><li>Inhibit prostaglandin synthesis </li></ul><ul><li>Vary in activity/potency </li></ul><ul>...
Cyclooxgenase inhibitors <ul><li>Fetal side effects: </li></ul><ul><li>Oligohydramnios </li></ul><ul><li>Premature closure...
Steroids <ul><li>Reduce risk of : </li></ul><ul><li>Respiratory distress syndrome </li></ul><ul><li>Intraventricular hemor...
Progesterone
Progesterone for the reduction of risk of preterm birth
Reduction of SPTBs By Progesterone Administration Among Asymptomatic High Risk Women <ul><li>60% reduction for births <...
Prevention of Recurrent Preterm Delivery by Progesterone Vaginal Gel-A R-DB-PC Trial ( O’Brien et al Ultrasound Obstet G...
<ul><li>It is possible that progesterone administration in women with history of SPTB may benefit only those with a shor...
Use of Progesterone to Reduce Preterm Birth (ACOG Committee Opinion, Number 419, October 2008) <ul><li>It should be offe...
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Preterm Labor by Yinka Oyelese

Published on: Mar 4, 2016
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Transcripts - Preterm Labor by Yinka Oyelese

  • 1. Preterm Birth Yinka Oyelese, MD, MRCOG Associate Professor, Maternal Fetal Medicine UTHSC
  • 2. Preterm birth rates in the United States < 37 weeks 12.9% %
  • 3. Preterm birth in the US One preterm birth every minute!
  • 4. To put it in perspective….. <ul><li>One preterm birth each minute </li></ul><ul><li>60 preterm births by the time this talk is over </li></ul><ul><li>Healthy people 2010 objective is to reduce rate to 7.6% </li></ul>
  • 5. Preterm birth <ul><li>75-80% of all perinatal mortality </li></ul><ul><li>50% of all long term neurodevelopmental morbidity </li></ul><ul><li>Tremendous financial, emotional burden on society </li></ul>
  • 6. <ul><li>Infants born preterm are at increased risk of: </li></ul><ul><li>Respiratory Distress syndrome </li></ul><ul><li>Chronic lung disease </li></ul><ul><li>Intraventricular hemorrhage </li></ul><ul><li>Necrotizing enterocolitis </li></ul><ul><li>Retinopathy of prematurity </li></ul><ul><li>Severe brain injury </li></ul>Newborn morbidity
  • 7. 50% of long term major morbidity among non-anomalous fetuses: <ul><li>Cerebral palsy </li></ul><ul><li>Mental retardation </li></ul><ul><li>Blindness </li></ul><ul><li>Deafness </li></ul><ul><li>Sensory deficits </li></ul><ul><li>Developmental delay </li></ul>Long term consequences
  • 9. Costs affect insurance rates, taxes, and PAY CHECKS!
  • 10. Sources of preterm birth, United States 2000 Ananth et al, Obstet Gynecol, 2006 Overall (%) Singletons (%) Twins (%) Spontaneous 60 69 44 Medically indicated 40 31 56
  • 11. Preterm births in the United States
  • 12. Spontaneous PTB Medically indicated PTB Preterm PROM
  • 13. SPB Source of Preterm Birth Tucker et al. Obstet Gynecol 1991 Spontaneous 30-50% Preterm PROM 30-40% Indicated 20-30%
  • 14. Medically indicated Spontaneous Overall SROM
  • 15. Preterm Birth Changes between 1989-00, US Whites Blacks All PTB 14% 15% Spont PTB 3% 27% Med-ind 55% 32% PNM 30% 25%
  • 16. Preterm Birth Trends Whites (%) Blacks (%) 89 00 Δ % 89 00 Δ % Total PTB 8.3 9.4 14 18.5 16.2 -15 pPROM 1.1 0.8 -23 2.3 1.5 -37 Med-ind 2.3 3.6 55 4.1 5.6 32 Spt labor 4.9 5.0 3 12.1 9.1 -27
  • 17. Indicated Preterm Birth Tucker et al. 1991 Meis et al. 1986 Singletons Twins Preeclampsia 43% 44% FGR/fet dist 37% 33% Abruption 7% 9% Fetal death 7% 7%
  • 18. Ananth and Vintzileos AJOG 2006 Ischemic Placental Disease Among… Ischemic placental disease present in Term births 1 in 10 births Preterm births 1 in 4 births Indicated preterm births ≥ 1 in 2 births
  • 20. Etiologies Stress Infection Bleeding Uterine overdistension
  • 21. <ul><li>Preterm birth is a “syndrome” </li></ul><ul><li>Inflammation/Infection (~40%) </li></ul><ul><li>Maternal/fetal stress (~25%) </li></ul><ul><li>Uteroplacental ischemia (~25%) </li></ul><ul><ul><li>Thrombophilia, decidual hemorrhage, abruption </li></ul></ul><ul><li>Abnormal uterine distension (~10%) </li></ul>
  • 22. Some pathways through which preterm birth may occur
  • 23. Some pathways through which preterm birth may occur
  • 24. Risk factors <ul><li>Prior preterm birth </li></ul><ul><li>Poor socio-economic status </li></ul><ul><li>Black race </li></ul><ul><li>Low education </li></ul><ul><li>Smoking </li></ul><ul><li>Bleeding </li></ul><ul><li>Assisted reproduction </li></ul><ul><li>Multiple gestation </li></ul><ul><li>Genital tract infections </li></ul><ul><li>Periodontal disease </li></ul><ul><li>Cervical surgery </li></ul><ul><li>Pregnancy termination </li></ul><ul><li>Uterine anomalies </li></ul>
  • 25. Preterm babies are more likely to have preterm births as adults Porter et al. Obstet Gynecol 1997;90:63-67 <ul><li>1405 preterm mothers </li></ul><ul><li>2781 term mothers </li></ul>
  • 26. Maternal and Paternal Influences <ul><li>77,452 boys and girls in Norway who later became parents </li></ul><ul><li>Gestational age of the child at birth increased </li></ul><ul><ul><li>0.58 days for each additional week in the father’s GA </li></ul></ul><ul><ul><li>1.22 days for each additional week in the mother’s GA </li></ul></ul>Lie et al. Obstet Gynecol 2006
  • 27. Recurrence of preterm birth
  • 28. Recurrence of preterm birth
  • 30. Average length of gestation by plurality
  • 31. <ul><li>Over 80% of patients who present with regular painful contractions go on to deliver at term </li></ul><ul><li>Most interventions do not prevent preterm birth and are potentially harmful </li></ul><ul><li>How then do we determine who will actually deliver preterm (isn’t THAT the question?) </li></ul>
  • 32. More than 1/2 of patients who deliver preterm have no risk factors More than 2/3 of patients with traditional risk factors do not deliver preterm Most important traditional risk factor is preterm delivery in a prior pregnancy
  • 33. Fetal fibronectin
  • 35. Fetal fibronectin
  • 40. Cervical Length as Predictor of SPB <ul><li>The risk of SPB is increased in women with short cervix. Abnormal cervical length < 25 mm (10%ile) (Iams JD & NICHD MFMU Network, 1996) </li></ul><ul><li>The shorter the cervix, the higher is the risk for SPB </li></ul>Conspiracy?
  • 44. Transvaginal sonographic cervical assessment
  • 45. Interventions that have been used <ul><li>Bed rest </li></ul><ul><li>Intravenous hydration </li></ul>
  • 46. Are there any therapeutic interventions to prevent SPTB?
  • 47. Types of Cervical Cerclage <ul><li>History-indicated </li></ul><ul><li>Physical exam-indicated </li></ul><ul><li>Ultrasound-indicated </li></ul>
  • 48. The Use of Cervical Cerclage for a Short Cervix ( Ultrasound-Indicated Cerclage ) 4 RCT’s <ul><li>Rust-2000 Unselected No benefit </li></ul><ul><li>Althuisius-2001 High-risk Benefit* </li></ul><ul><li>To-2004 Unselected No benefit </li></ul><ul><li>Berghella-2004 Unselected No benefit </li></ul>AUTHOR-YEAR POPULATION OUTCOME * REDUCTION OF PREMATURITY, MORTALITY & MORBIDITY
  • 49. Multicenter RCT on the Use of Cervical Cerclage in High Risk Pregnancies (Report of the MRC/RCOB, Br J Obstet Gynaecol 1993; 100:516) <ul><li>Benefit observed in 1:25 cases </li></ul><ul><li>Cerclage is beneficial only in women with a history of > 3 second trimester losses/preterm births </li></ul>History-Indicated Cerclage
  • 50. Cerclage for dilated cervix with membranes at or beyond the external os Althusius et al, Am J Obstet Gynecol 2003 Cerclage & Indomethacin (n=13) Bedrest alone (n=10) Prolongation (weeks) 7.7 3.0 Neonatal survival 56% 28% Preterm birth <34 weeks 54% 100% Composite neonatal morbidity 62% 100%
  • 51. Management of Cervical Insufficiency and Bulging Fetal Membranes (at 18-26 weeks) (Daskalakis et al Obstet Gynecol 2006;107:219) <ul><li>Prolongation (wks) 8.8 3.1 </li></ul><ul><li>Mean BW (g) 2,101 739 </li></ul><ul><li>Live birth 86% 41% </li></ul><ul><li>Neon survival 96% 57% </li></ul><ul><li>PTB <32 wks 31% 94% </li></ul><ul><li>NICU admission 28% 86% </li></ul>Cerclage (n=29) No Cerclage (n=17) Physical Exam-Indicated Cerclage
  • 52. Use of Cerclage for Prevention of SPB in Women With Prior SPB. A Meta-analysis of 4 RCTs (Berghella V, Odibo A, To M, Rust O and Althiusius S) Obstet Gynecol 2005;106:181 <ul><li>4 RCTs (n=208 women with prior SPB) </li></ul><ul><li>SPB <35 weeks </li></ul><ul><li>No cerclage 39/101 (39%) </li></ul><ul><li>Cerclage (for CL <25 mm) 25/107 (22%) </li></ul><ul><li> RR=0.61 (95% CI=0.40, 0.92) </li></ul><ul><li>(Hx of prior 2 nd trim loss) RR=0.57 (95% CI=0.33, 0.99) </li></ul>
  • 53. Multicenter Randomized Trial of Cerclage For Preterm Birth Prevention In High-Risk Women With Shortened Mid-Trimester Cervical Length (Owen J, Abst #4, Am J Obstet Gynecol Suppl Dec 2008) Reduction in PTB < 35 wks in cerclage patients OR (95% CI) If CL < 15 mm 0.23 (0.08, 0.66) If CL 16-24 mm 0.84 (0.49, 1.40) P=0.05 CONCLUSION: Cerclage will mostly benefit high-risk women with mid-trimester CL < 15 mm (77% reduction in PTB rate)
  • 54. Tocolytics <ul><li> -adrenergic agents </li></ul><ul><li>Magnesium sulfate </li></ul><ul><li>Prostaglandin synthetase inhibitors </li></ul><ul><li>Calcium channel blockers </li></ul><ul><li>Nitroglycerin </li></ul><ul><li>Oxytocin antagonists </li></ul>
  • 55. Magnesium sulfate! Good or evil?
  • 56. Contraindications to Tocolysis <ul><li>Conditions where delivery is indicated such as </li></ul><ul><li>Severe preeclampsia/hypertension </li></ul><ul><li>Fetal non-reassuring status </li></ul><ul><li>Maternal non-reassuring status </li></ul><ul><li>Significant hemorrhage </li></ul><ul><li>Maternal cardiac disease </li></ul><ul><li>Gestational age >36 weeks (? >34 weeks) </li></ul><ul><li>Infection/ chorioamnionitis </li></ul><ul><li>Fetal demise or lethal anomaly </li></ul>
  • 57. Goals of tocolysis <ul><li>To allow steroid administration </li></ul><ul><li>To allow transport or to facilitate delivery under safer circumstances </li></ul><ul><li>To prolong gestation in very preterm pregnancies </li></ul>
  • 58. Calcium channel blockers <ul><li>Inhibit calcium entry into cells </li></ul><ul><li>Nifedipine most commonly used </li></ul><ul><li>Rapidly absorbed after oral adminstration </li></ul><ul><li>Peak concentration in 15-90 minutes </li></ul><ul><li>Half life of 81 minutes </li></ul><ul><li>Duration of action of single dose 6 hours </li></ul><ul><li>Good contraction suppression and few side effects </li></ul><ul><li>12 reported trials show reduced deliveries within 7 days (RR 0.76; CI 0.60, 0.97) </li></ul><ul><li>Reduced deliveries before 34 weeks (RR 0.83, CI 0.69, 0.99) </li></ul><ul><li>Reduced fetal RDS, IVH, NEC, jaundice, when compared with other tocolytics </li></ul><ul><li>Fewer women stop treatment due to side effects </li></ul>
  • 59. Calcium channel blockers <ul><li>Side effects: </li></ul><ul><li>Hypotension </li></ul><ul><li>Headaches </li></ul><ul><li>Dizziness </li></ul><ul><li>Nausea </li></ul><ul><li>No significant fetal effects </li></ul><ul><li>Administration </li></ul><ul><li>10 -20 mg every 4-6 hours </li></ul>
  • 60. Cyclooxgenase inhibitors <ul><li>Inhibit prostaglandin synthesis </li></ul><ul><li>Vary in activity/potency </li></ul><ul><li>Indomethacin most widely used </li></ul><ul><li>Powerful tocolytic </li></ul><ul><li>Crosses placenta </li></ul><ul><li>Associated with reduction in births before 37 weeks, increased gestational age, birth weight </li></ul><ul><li>Maternal side effects: </li></ul><ul><li>GI disturbances </li></ul><ul><li>Bleeding </li></ul><ul><li>Thrombocytopenia </li></ul><ul><li>Asthma </li></ul><ul><li>Renal injury </li></ul>
  • 61. Cyclooxgenase inhibitors <ul><li>Fetal side effects: </li></ul><ul><li>Oligohydramnios </li></ul><ul><li>Premature closure of ductus arteriosus </li></ul><ul><li>These complications are rare </li></ul><ul><li>Generally not recommended beyond 37 weeks </li></ul><ul><li>NEC </li></ul><ul><li>Treatment protocol </li></ul><ul><li>50 mg loading </li></ul><ul><li>25-50 mg every 6 hours </li></ul><ul><li>Assess AFI, ductus if using for prolonged periods </li></ul><ul><li>Stop treatment if delivery is imminent </li></ul>
  • 62. Steroids <ul><li>Reduce risk of : </li></ul><ul><li>Respiratory distress syndrome </li></ul><ul><li>Intraventricular hemorrhage </li></ul><ul><li>Necrotizing enterocolitis </li></ul>
  • 63. Progesterone
  • 64. Progesterone for the reduction of risk of preterm birth
  • 65. Reduction of SPTBs By Progesterone Administration Among Asymptomatic High Risk Women <ul><li>60% reduction for births < 37 weeks-daily 100mg progesterone vaginal suppositories (da Fonseca et al, Am J Obstet Gynecol 2003;188:419) </li></ul><ul><li>34% reduction for births < 37 weeks-weekly IM injections of 17-P (Meis PJ & NICHD MFMU Network, N Engl J Med 2003;348:2379) </li></ul>CL unknown (was not reported) in the above two studies
  • 66. Prevention of Recurrent Preterm Delivery by Progesterone Vaginal Gel-A R-DB-PC Trial ( O’Brien et al Ultrasound Obstet Gynecol 2007;30:687 DeFranco et al Ultrasound Obstet Gynecol 2007;30:697) <ul><li>N=659 women with Hx of SPTB </li></ul><ul><li>No reduction in PTB at < 32 weeks </li></ul><ul><li> (SECONDARY ANALYSIS) </li></ul><ul><li>Women with CL <28 mm had </li></ul><ul><li>a) less PTBs (0% vs, 30%); and </li></ul><ul><li>b) less NICU admissions (16% vs. 52 %) </li></ul>Daily vag prog gel (90mg) starting at 18-23 weeks
  • 67. <ul><li>It is possible that progesterone administration in women with history of SPTB may benefit only those with a short cervix in the current pregnancy </li></ul>Speculation
  • 68. Use of Progesterone to Reduce Preterm Birth (ACOG Committee Opinion, Number 419, October 2008) <ul><li>It should be offered to women with a singleton pregnancy and a history of spontaneous preterm birth < 37 weeks gestation </li></ul><ul><li>Progesterone supplementation for asymptomatic women with an incidentally identified very short cervical length (< 15 mm) may be considered; however, routine cervical length screening is not recommended </li></ul>