Preterm labour

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A powerpoint presentation on pereterm labor and delivery by Dr Max Mongelli, Nepean Hospital, NSW

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Preterm labour

  1. 1. Preterm Labour Max Mongelli Western Clinical School University of Sydney Nepean Hospital
  2. 2. DefinitionsThreatened pre-term labourPre-term labourPre-term delivery
  3. 3. IncidenceApprox 5-6% in AustraliaMore than 10% in the USASecond leading cause of mortality after congenital anomalies
  4. 4. Risk Factors (1)StressOccupational fatigueSmoking/substance abusePoor antenatal care
  5. 5. Risk Factors (2)Excessive or impaired uterine distension: Multiple pregnancy Polyhydramnios Fibroids Uterine anomaly
  6. 6. Risk Factors (3)Cervical factors: History of second trimester loss Cervical surgery Premature cervical dilatation or effacement
  7. 7. Risk Factors (4)Infections: Systemic infections STDs Pyelonephritis Bacteriuria Periodontal disease
  8. 8. Risk Factors (5)Fetal & placental factors: Congenital anomalies IUGR Abruption Vaginal bleeding Placenta previa
  9. 9. Causes of Preterm LabourMajor focus of O & G research.80% spontaneous onset 50% PTL 30% PPROM20% due to to intervention for maternalor fetal indications
  10. 10. Four Major CategoriesActivation of hypothalamic/pituitary/adrenal axis: maternal or fetalInflammationDecidual hemorrhageUterine over-distention
  11. 11. Activation of HPA AxisMaternal physical/emotional stressPlacental vasculopathyIncreased secretion of CRH – fetal ACTHIncreased secretion placental estrogenIncreased secretion of placental PGsActivation of myometrium
  12. 12. InflammationBoth systemic and genital tract infectionsChorioamnionitis in 50% of preterm laboursbefore 30 weeks gestationCan occur with intact membranesRaised cytokines (interleukins, TNF, GSF)Enhanced prostaglandin production
  13. 13. BacteriaSome organisms have a direct role in PTLindependent of inflammatory mediatorsPsudomonas, staph, strep, bacteroides,enterobacter produce proteases that can breakdown fetal membranesCan also produce phospholipase A2 andendotoxins, stimulating uterine contractions
  14. 14. BacteriaIncreased rates of PTL noted in women withGBS, chlamydia and syphilisRisk of PTL reduced by treating: Asymptomatic bacteriuria Gonorrhea BV in high risk patients for PTL
  15. 15. Oral BacteriaIncreased rates of PTL noted in women withperiodontal disease? intrauterine infection following “descent”from oral cavityCase report: Bergeyella bacterium isolatedfrom both the mouth and amniotic fluid ofpatient with intact membranes having PTL at24 weeks
  16. 16. Decidual hemorrhageVaginal bleeding in more than one trimesterincreases risk of PTL 7-foldPlacental histopathology: occult decidualhemorrhage noted in 36-38% of cases of PTBPPROM may be related to high concentrations oftissue factor
  17. 17. Decidual hemorrhageDecidual TF combines with FVIIa to activateFX, to generate thrombinThrombin is a potent inducer of IL8, causinglocalised inflammatory reactions.Leads to degradation of fetal membraneextracellular matrix, PPROM
  18. 18. Uterine Over-distentionUp-regulation of oxytocin receptorsFormation of gap junctionsPGE2 and PGFMyosin light chain kinase
  19. 19. Uterine Over-distention Polyhydramnios Multiple pregnancy
  20. 20. Cervical IncompetenceIn most cases a secondary effectCervical cone biopsyLLETZ, laser coneIncreased risk of PTL - < 37 weeks: OR 3.4 <32 weeks: OR 4.6 <28 weeks: OR 12.4
  21. 21. Prevention of Preterm Labour
  22. 22. Potentially effective interventionsProgesterone supplementsSmoking cessationAvoidance of drugs & alcoholReduce rate of multiple pregnancyCervical cerclageReduce occupational stressNutritionEarly diagnosis & treatment of infection
  23. 23. Progesterone supplementsMost trials use 17-alpha-hydroxyprogesteronecaproate, weekly IMIReduction in PTL rates by 15-70%Most effective in women with previous PTL at<34 weeksIncreased risk of GDM (OR 2.9)ACOG recommends use in women with previousPTL onlyNo reduction in perinatal mortalityMore research needed
  24. 24. Stop smokingCigarette smoking has a dose-dependentrelationship with preterm labourPartially due to smoking-related complicationsCessation of smoking likely to be beneficial, butnot proven in RCT’s
  25. 25. Avoidance of drugs and alcohol Cocaine Alcohol ? Cannabis
  26. 26. Reduction in multiple pregnancies Multiple pregnancies six times more likely to deliver preterm Risk increases with increasing no. of fetuses Valid indication before starting ART Limit no. of embryos transferrred
  27. 27. Cervical CerclageCervical incompetence based on history orultrasound findingsRCOG study of 1292 womenSignificant reduction in preterm births<33weeksNNT = 25 cerclagesIncreased risk of puerperal infectionIncreased risk of PTL in twins
  28. 28. Reduction of Work FatigueExcessive physical demands related toincreased risk (OR 1.63)Working > 42 hrs/weekStanding > 6 hrs/dayLow job satisfactionNo RCT’s available
  29. 29. Nutritional interventionsNo fish consumption linked to excess risk ofPTL (OR 19.6)Fish oil supplements: one multi-centre RCT inhigh risk women showed a significantreduction in PTL (OR 0.54)Trial with docosahexanoic acid supplements:significant prolongation of pregnancyCARRDIP trial: marked reduction in risk ofpreterm labour (1/141 vs 11/149)
  30. 30. Early detection and treatment of infectionAsymptomatic bacteriuria: treatment significantlyreduces risk of PTL or LBW infants (OR 0.60)Chlamydia, gonorrhea, BV: routine screening notindicatedWomen with previous PTL and +ve for BV maybenefit from treatmentTrichomonas: treatment of asymptomatic women mayincrease risk of PTL
  31. 31. Case Scenario 119 yo G3P1M1 late booking at 22 weeksPrevious preterm delivery at 29 weeksHeavy smoker, nil alcoholWorks in supermarket as check-outassistant, prolonged standingOffensive vaginal discharge
  32. 32. Case Scenario 235 yo G5P1M3 booking at 9 weeksPrevious preterm delivery at 27 weeks dueto placental abruptionThree first trimester miscarriagesFamily history of thromboembolism
  33. 33. Diagnosis of Preterm LaborNo universally accepted definitionRegular uterine contractions andCervical dilatation or effacement
  34. 34. Tests for Prediction of Preterm DeliveryCervico-vaginalfibronectinUltrasoundmeasurement ofcervical length
  35. 35. Treatment of Preterm LaborNo generally accepted criteria forstarting tocolysisAbout 30-50% of threatened pretermlabours spontaneously resolveTreat the underlying cause if possible
  36. 36. General MeasuresNo proven benefits for: Bed rest Hydration Sedation
  37. 37. Objectives of TocolysisDelay delivery so that steroids may begivenAllow safe transport of the mother ifpossibleProlong pregnancy when there are self-limiting causes of labour e.g. sepsis
  38. 38. Contraindications to Tocolysis APH with hemodynamic instability Severe pre-eclampsia/eclampsia Chorioamnionitis Severe IUGR Evidence of fetal compromise Lethal fetal anomaly Fetal demise
  39. 39. Benefits of Antenatal SteroidsReduce risk of: RDS (RR 0.66) NEC (RR 0.46) IVH (RR 0.54) Severe bruising Systemic infection in the first 48 hr of life (RR 0.56) Admission to NICU (RR 0.80) Neonatal mortality (RR 0.69)
  40. 40. Antenatal SteroidsEffective in women with SROM and PETMaximum effect at 48 hrsBetamethasone 11.4 mg IM 12 hrs apartBeneficial effects wear off after 2 weeksNo significant maternal side effects
  41. 41. TOCOLYTIC AGENTSBetamimetic agentsNifedipineNSAIDSAtosibanMagnesium sulphate
  42. 42. BETA-ADRENERGIC RECEPTOR AGONISTS
  43. 43. BETA-ADRENERGIC RECEPTOR AGONISTSMechanism of action: Cause myometrial relaxation by binding with beta-2 receptors and increasing intracellular adenyl cyclase. Drop in intracellular calcium Target cells eventually become desensitized to the effect of beta-adrenergic agonists (tachyphylaxis).
  44. 44. BETA-ADRENERGIC RECEPTOR AGONISTS: EFFICACYMeta-analyses: Reduction in no. of births within 48 hrs (RR 0.63). No decrease in no. of births within 7 days No change in perinatal mortality Marginal decrease in RDS cases
  45. 45. BETA-ADRENERGIC RECEPTOR AGONISTS: MATERNAL SIDE EFFECTS Tachycardia Palpitations Lowered blood pressure SOB Myocardial ischemia Pulmonary oedema (0.3%) Hyperglycemia, hypokalemia
  46. 46. BETA-ADRENERGIC RECEPTOR AGONISTS: FETAL SIDE EFFECTS Tachycardia Neonatal hypoglycemia
  47. 47. TERBUTALINE: DOSAGEContinuous iv infusion (2.5 mcg/minincreased to max. of 25 mcg/min)S.C.I. 25 mg statStop if HR>120 or symptomaticMonitor K+ and BSL
  48. 48. CALCIUM CHANNEL BLOCKERSBlock the influx of Ca+ through thecell membraneReduction of intracellular free calciumInhibition of myosin light chain kinasephosphorylationRelaxation of uterine muscle
  49. 49. EFFICACY OF NIFEDIPINEMeta-analysis of 12 RCT’s: Reduction in no. of births within 7 days (RR 0.76) Reduction in no. of births before 34 weeks (RR 0.83) Lower risk of RDS (RR 0.63), NEC (RR 0.23), IVH (RR 0.59), jaundice (RR 0.73) Fewer maternal side effects (RR 0.14)
  50. 50. NIFEDIPINE : MATERNAL SIDE EFFECTSPeripheral vasodilator: Nausea, flushing, headache Palpitations Reduction in MAP, reflex tachycardia Rarely severe hypotension
  51. 51. NIFEDIPINE : FETAL SIDE EFFECTSAnimal studies: reduced uterine andumbilical blood flowNo evidence of toxicity in humans
  52. 52. NIFEDIPINE : CONTRAINDICATIONSKnown allergyLV dysfunction or cardiac failureHepatic dysfunctionConcomitant use of magnesium: respiratory paralysis
  53. 53. NIFEDIPINE : DOSAGEHalf-life 2-3 hrs, single dose lasts up to 6 hrs20 mg po statRepeat 30 mins later if still contractingMaintenance 20-40 mg qidMax dose 160 mg in 24 hrs
  54. 54. ROUTINE ANTIBIOTICS IN PRETERM LABOUR WITH INTACT MEMBRANESResults of ORACLE and meta-analysis: No improvement in neonatal outcomes Reduction in maternal infection (RR 0.74) Uncertainty about optimal antibiotics and regime
  55. 55. MANAGEMENT FOLLOWING SUCCESSFUL TOCOLYSISOptimal approach unknown – limited data Prolonged hospitalisation probably of no value Bed rest not proven effective Avoid physically demanding work
  56. 56. MANAGEMENT FOLLOWING TOCOLYSIS: SEXUAL ACTIVITY Observational data only Higher mortality amongst infected infants associated with recent coitus: 11% vs 2.4% Increased rates or RDS, jaundice, low Apgar scores (x 2) Effect stronger among preterm births Prudent to suggest avoidance of coitus after successful tocolysis
  57. 57. MANAGEMENT FOLLOWING TOCOLYSIS: MAINTENANCE TOCOLYSIS Most RCT’s are small Endogenous prostaglandins may increase oxytocin receptor density Cochrane review of maintenance oral beta- agonists: no significant benefits May be useful for temporary relief of painful contractions
  58. 58. MANAGEMENT FOLLOWING TOCOLYSIS: REPEATED COURSES OF ANTENATAL STEROIDS Repeat courses of steroids improve neonatal pulmonary outcomes, especially in earlier gestational ages Evidence of delayed neuronal maturation and increased risk of IUGR in animal studies Humans: reduced birth weight only with 4 or more courses Catch-up growth by time of discharge from hospital
  59. 59. MANAGEMENT FOLLOWING TOCOLYSIS: REPEATED COURSES OF ANTENATAL STEROIDS Long-term neuro-developmental data not available Optimal number of courses of steroids unknown Two courses probably safe
  60. 60. MANAGEMENT FOLLOWING TOCOLYSIS: RISK OF IUGR Threatened PTL may be an indication of fetal stress arising from unfavourable intrauterine environment. Placental pathology: increased incidence of fetal or maternal vascular lesions without inflammation Risk of giving birth to SGA infant (OR 2.2) Need closer surveillance with USS for growth and Doppler studies
  61. 61. CASE SCENARIO 333 y.o G1P0 presents to rural hospital at 31weeksStrong, painful contractions for 3 hoursSlight brownish PV lossNormal recordings; cephlic presentationCTG “irritable uterus” patternCervix 2 cm long os closedHow would you manage?
  62. 62. CASE SCENARIO 421 y.o G2P1 at 29 weeks recently dischargedfrom hospital following TPL successfullystopped with nifedipineCompleted course of steroidsSingle mother, smokes 20/dayHow would you manage her?

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