1. Preterm Labor: Evidence Based View

2. Evidence Based Sources:
PubMed
Cochrean library
RCOG Guidelines
ACOG Issues Guidelines
National Guideline Clearinghouse
MOH Sing. Guideline

3. Definition
Preterm labor is the presence of contractions of sufficient strength and frequency to effect progressive effacement and dilation of the cervix between 20 and 37 weeks' gestation
WHO

4. Preterm Labor Incidence : 6- 10% Spontaneous : 40-50% PROM : 25-40%
Obstetrically indicated : 20-25%

5. Preterm Labor
Most mortality and morbidity is experienced by babies born before 34 weeks.

6. Major Risks Of Preterm Delivery
Death
Respiratory distress syndrome
Hypothermia
Hypoglycaemia
Necrotising enterocolitis
Jaundice
Infection
Retinopathy of prematurity
Goldenberg , Obstetrics &Gynecology

7. Can preterm labor be predicted?

8. Prediction Assessment of risk factors
Vaginal examination to assess the cervical status
Ultrasound visualization of cervical length and dilatation
Detection of foetal fibronectin in cervicovaginal secretions

9. 1-Risk Factors
While the exact cause of preterm labor is often unknown, there is strong evidence that intrauterine infection may play a role in very early preterm labor.
ACOG NEWS RELEASE November 2002

10. 1-Risk Factors Bacterial Vaginosis
Bacterial vaginosis increased the risk of preterm delivery >2-fold .
Leitich et al Am J Obstet Gynecol Jul;189(1):139 ( Meta-Analysis)

11. 1-Risk Factors Other Risk Factors Multiple pregnancy: risk >50%
Previous preterm delivery: risk %
Cigarette smoking: risk 20-30%
Cervical incompetence
Uterine abnormalities
MOH Sing. Guideline Grade C Recommendation 2001

12. 1-Risk Factors Other Risk Factors
Young age of mother - less than 16 years of age.
•Lower socioeconomic class.
Reduced body mass index (BMI) - BMI less than 19.0.
Antiphosphlipid syndrome.
Obstetric complications, including hypertension in pregnancy,antepartum haemorrhage, infection, polyhydramnios, foetalabnormalities.
MOH Sing. Guideline Grade C Recommendation 2001

13. 2-Vaginal examination
Digital examination is the traditional method used to detect cervical maturation, but quantifying these changes is often difficult.

14. 3-Vaginal U/S
Vaginal ultrasonography allows a more objective approach to examination of the cervix.
Goldenberg , Obstetrics &Gynecology

15. 4-Fibronectin Test Outcome Sensitivity specificity 52% 85%
Delivery <37
53%
89%
Delivery <34
71%
Delivery within 1 Week
89%
Delivery within 2 Week
67%
89%
Delivery within 3 Week
59%
92%
Leitich & Kaider ,BJOG Apr;110 , 20: Meta-Analysis 40 studies

16. Prevention

17. Prevention of Preterm Labor
Women at increased risk of preterm delivery may be identified by various risk factors in the obstetric history and treated.
American Academy of Pediatrician & ACOG 1997

18. 17 Hydroxy -Progesterone Caproate
Prophylactic use of 17 hydroxy progesterone caproate to prevent preterm labor revealed a significant decrease in preterm birth .
However, it has not successfully inhibited active preterm labor.
Keirse. Br J Obstet Gynaecol 1990;97: Meta-anlysis of 6RCTs.
Meis et al. N Engl J Med Jun 12;348(24): RCT (19 centers )

19. Treatment Of Vaginosis
Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the 2nd trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth.
Ugwumadu et al. Lancet Mar 22;361: ) RCT

20. Diagnosis

21. Diagnosis > 2- Cervical dilatation > 1 cm 3- Effacement _ 80%.
3 criteria to document PTL(20-37w)
1-Regular uterine contractions occur at 4/20 min. or 8/60 min. Plus: progressive change in the cervix.
2- Cervical dilatation > 1 cm
3- Effacement _ 80%.
>
American Academy of Pediatrician & ACOG 1997

22. Vaginal U/S+ Fibronectin Test
Suspected preterm labor with no cervical changes :
Negative fetal fibronectin +
Cervical length > 30 mm
the likelihood of delivering in the next week is less than 1%.
Thus most women with a negative test can safely be sent home without treatment.
Goldenberg , Obstetrics &Gynecology

23. Treatment
Inhibition of labor
Corticosteroid
Antibiotics
Others.

24. Inhibition Of Labor
Bed rest :DVT
Hydration &sedation
Tocolytics

25. Most Efforts to Prevent Preterm Labor Not Effective
Until effective strategies are found, efforts should be aimed at preventing newborn complications by :
Corticosteroids
Antibiotics against group B strep
Avoiding traumatic deliveries.
Delivery in a center with experienced resuscitation teams and neonatal intensive care
ACOG NEWS RELEASE: November 2002

26. Incidence of preterm birth in USA, 1981-1999.
National Center for Health Statistics. Goldenberg.. Obstet Gynecol 2002

27. Hydration
Intravenous hydration does not seem to be beneficial, even during the period of evaluation soon after admission,
Women with evidence of dehydration may, however, benefit from the intervention.
Stan et al (Cochrane Review 2000). In: The Cochrane Library, Issue Oxford

28. Is Tocolysis Better Than No Tocolysis For Preterm Labour?
It is reasonable not to use tocolytic drugs, as there is no clear evidence that they improve outcome. However, tocolysis should be considered if the few days gained would be put to good use, such as completing a course of corticosteroids, or in utero transfer
RCOG Guideline Grade A recommendation 2002 (Valid:2005)

29. Tocolytics
Most authorities do not recommend use of tocolytics at or after 34 weeks' .
There is no consensus on a lower gestational age limit for the use of tocolytic agents.
Goldenberg , Obstetrics &Gynecology

30. Choice Of Tocolytic Drug
B –Sympathomimetic (Ritodrine)
Magnesium sulphate
Indomethacin
Nifedipine = Epilate
Atosiban= Tractocile

31. Choice Of Tocolytic Drug
If a tocolytic drug is used, ritodrine no longer seems the best choice.
Atosiban or nifedipine appear preferable as they have fewer adverse effects and seem to have comparable effectiveness.
RCOG Guideline Grade A recommendation 2002 (Valid:2005)

32. B -Sympathomimetic Agents.
Use of beta-agonists should be restricted to the management of preterm labour between 20 and 35 completed weeks, including women with ruptured membranes. (Grade A)
RCOG Guideline Grade A recommendation 1997

33. Valid until October 2005 unless otherwise indicated
Clinical Green Top Guidelines
Tocolytic Drugs for Women in Preterm Labour (1B)
(Replaces Guideline No.1A Beta-agonists and No.1 Ritodrine)
Valid until October unless otherwise indicated
                                             

34. B -Sympathomimetic Agents.
Maternal: pulmonary edema, myocardial ischemia, arrhythmia, and even maternal death.
Fetal : arrhythmia, cardiac septal hypertrophy , hydrops, pulmonary edema, and cardiac failure. hypoglycemia, periventricular-intraventricular hemorrhage, and fetal and neonatal death. .

35. Magnesium Sulfate
Magnesium sulphate is ineffective at delaying birth or preventing preterm birth, and its use is associated with an increased mortality for the infant.
Crowther et al, (Cochrane Review) August In: The Cochrane Library, Issue Oxford: Update Software.

36. Nitric Oxide Donors
There is insufficient evidence to support the routine administration of nitric oxide donors (nitroglycerin )in the treatment of preterm labor.
Duckitt& Thornton , (Cochrane Review) March In: The Cochrane Library, Issue Oxford: Update Software.

37. Indomethacin
Compared with ritodrine there is insufficient evidence for any differential effect on delay in delivery, but indomethacin does seem to have fewer maternal adverse effects than the beta-agonists
RCOG Guideline Grade B Recommendation 2002 (Valid:2005)

38. Indomethacin Fetal risk: Premature closure of the ductus.
Renal and cerebral vasoconstriction.
Necrotising enterocolitis
Common with high dose and prolonged exposure.
RCOG Guideline Grade B Recommendation 2002 (Valid:2005)

39. Indomethacin Indomethacin therapy for < 48 hours
< weeks' gestation)
Not > 200mg/day.
appears to be a relatively safe and effective tocolytic agent
Goldenberg , Obstetrics &Gynecology

40. Indomethacin
Indomethacin can be used as a second-line tocolytic agent in early gestational age preterm labors.
Goldenberg , Obstetrics &Gynecology

41. Indomethacin Indomethacin may be a first-line tocolytic in:
Associated polyhydramnios :
( to have renal effects of indomethacin)
Newton eMedicine 2002

42. Indomethacin 50 mg Loading dose Then 25-50mg /6hs Capsule 25mg oral
Amp mg
Rectal Supp mg
50 mg Loading dose
Then 25-50mg /6hs
Newton eMedicine 2002

43. Atosiban: Tractocil
Atosiban, a synthetic peptide, is a competitive antagonist of oxytocin at uterine oxytocin receptors.

44. Atosiban: Tractocil Atosiban - compared with beta-agonists- has:
Little difference in the effect of these agents on delayed delivery
Fewer maternal adverse effects than beta-agonists, such as chest pain, palpitations , tachycardia , hypotension , dyspnoea ,vomiting , and headache.
Worldwide Atosiban Vs Beta-agonists Study Group. BJOG 2001;108:133–42( RCT)

45. Nifedipine Nifedipine- compared with ritodrine - has:
Higher delaying of delivery for >48 H.
Lower risk of RDS &Neonatal jundice.
Lower admission to NN ICU
Fewer maternal adverse effects
Tsatsaris et al, . Obstet Gynecol 2001;97:840–7. (Meta-analysis)

46. Nifedipine
When tocolysis is indicated for women in preterm labor, calcium channel blockers are preferable to other tocolytic agents compared, mainly betamimetics.
Further research should address the effects of different dosage regimens and formulations
King et al, (Cochrane Review) In: The Cochrane Library, Issue Oxford: Update Software.

47. Nifedipine 20mg initial 10-20 mg /4-6 h Epilate capsule :10mg
Epilate retard Tablet: 20 mg
Tsatsaris et al, . Obstet Gynecol 2001;97:840–7. (Meta-analysis)

48. Maintenance Tocolysis Is Not Recommended For Routine Practice.
There is insufficient evidence for any firm conclusions about whether or not maintenance tocolytic therapy following threatened preterm labor is worthwhile. Therefore maintenance therapy cannot be recommended for routine practice.
RCOG Guideline Grade A recommendation 2002 (Valid:2005)

49. Corticosteroids
Antenatal corticosteroids are associated with a significant reduction in rates of RDS, neonatal death and intraventricular haemorrhage, although the numbers needed to treat increase significantly after 34 weeks' gestation.
RCOG Guidelines : Grade A Recommendation

50. Corticosteroids
The optimal treatment-delivery interval for administration of antenatal corticosteroids is after 24 hours but < 7 days after the start of treatment.
RCOG Guidelines : Grade A Recommendation

51. Corticosteroids
Two 12 mg doses of betamethasone given IM 24 hours apart, Or
Four 6 mg doses of dexamethasone given IM 12 hours apart (I-A).
There is no proof of efficacy for any other regimen.
SOGC Recommendation Jan. 2003

52. Antibiotics
There is no evidence of clear overall benefit from prophylactic antibiotics for preterm labour with intact membranes on neonatal outcomes.
King & Flenady (Cochrane Review August 2002). In: The Cochrane Library, Issue Oxford: Update Software.

53. ACOG Advises Screening All Pregnant Women for Group B Strep.
Screening for GB Strep.
ACOG Advises Screening All Pregnant Women for Group B Strep.
ACOG NEWS RELEASE November 2002

54. Group B Streptococci (GBS) Prophylaxis
All patients in preterm labor are considered at high risk for neonatal GBS sepsis and should receive prophylactic antibiotics regardless of culture status.
Goldenberg , Obstetrics &Gynecology

55. Group B Streptococci (GBS) Prophylaxis
The goal of this strategy is to prevent neonatal sepsis, and not to prevent preterm birth.
Goldenberg , Obstetrics &Gynecology

56. Prophylactic Vitamin K Or Phenobarbital
Have not been shown to significantly prevent periventricular haemorrhages in preterm infants.
Crowther & Henderson-Smart (Cochrane Review Novemb ) In:The Cochrane Library, Issue Oxford: Update Software
Crowther & Henderson-Smart (Cochrane Review May 2003 ) In:The Cochrane Library, Issue Oxford: Update Software
Goldenberg , May 2003

57. Conclusions
Various strategies that have been used to prevent or treat preterm labor, haven't proven effective.
Tocolysis should be considered only for 2 days- if needed - for corticosteroids thereby , or in utero transfer to a tertiary center .

58. Conclusions
If a tocolytic drug is used, ritodrine no longer seems the best choice.

59. Conclusions
Other drugs with fewer adverse effects and comparable effectiveness are now recommended
Atosiban or nifedipine have been recommended by RCOG
endomethacin may be used as a 2nd line tocolytic or if there is polyhydramnous

60. Conclusions Maintenance tocolytic therapy has no proven effect.
It cannot be recommended for routine practice.

61. Thank You