Preterm Labor by Yinka Oyelese


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Preterm Labor by Yinka Oyelese

  1. 1. Preterm Birth Yinka Oyelese, MD, MRCOG Associate Professor, Maternal Fetal Medicine UTHSC
  2. 2. Preterm birth rates in the United States < 37 weeks 12.9% %
  3. 3. Preterm birth in the US One preterm birth every minute!
  4. 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. 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. 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. 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
  8. 9. Costs affect insurance rates, taxes, and PAY CHECKS!
  9. 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
  10. 11. Preterm births in the United States
  11. 12. Spontaneous PTB Medically indicated PTB Preterm PROM
  12. 13. SPB Source of Preterm Birth Tucker et al. Obstet Gynecol 1991 Spontaneous 30-50% Preterm PROM 30-40% Indicated 20-30%
  13. 14. Medically indicated Spontaneous Overall SROM
  14. 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%
  15. 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
  16. 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%
  17. 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
  18. 20. Etiologies Stress Infection Bleeding Uterine overdistension
  19. 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>
  20. 22. Some pathways through which preterm birth may occur
  21. 23. Some pathways through which preterm birth may occur
  22. 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>
  23. 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>
  24. 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
  25. 27. Recurrence of preterm birth
  26. 28. Recurrence of preterm birth
  27. 30. Average length of gestation by plurality
  28. 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>
  29. 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
  30. 33. Fetal fibronectin
  31. 35. Fetal fibronectin
  32. 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?
  33. 44. Transvaginal sonographic cervical assessment
  34. 45. Interventions that have been used <ul><li>Bed rest </li></ul><ul><li>Intravenous hydration </li></ul>
  35. 46. Are there any therapeutic interventions to prevent SPTB?
  36. 47. Types of Cervical Cerclage <ul><li>History-indicated </li></ul><ul><li>Physical exam-indicated </li></ul><ul><li>Ultrasound-indicated </li></ul>
  37. 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
  38. 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
  39. 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%
  40. 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
  41. 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>
  42. 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)
  43. 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>
  44. 55. Magnesium sulfate! Good or evil?
  45. 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>
  46. 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>
  47. 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>
  48. 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>
  49. 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>
  50. 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>
  51. 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>
  52. 63. Progesterone
  53. 64. Progesterone for the reduction of risk of preterm birth
  54. 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
  55. 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
  56. 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
  57. 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>