Preterm Labor: Evidence Based View

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

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

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

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

Major Risks Of Preterm Delivery Death Respiratory distress syndrome Hypothermia Hypoglycaemia Necrotising enterocolitis Jaundice Infection Retinopathy of prematurity Goldenberg , Obstetrics &Gynecology 11-2002

Can preterm labor be predicted?

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

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

1-Risk Factors Bacterial Vaginosis Bacterial vaginosis increased the risk of preterm delivery >2-fold . Leitich et al Am J Obstet Gynecol. 2003 Jul;189(1):139 ( Meta-Analysis)

1-Risk Factors Other Risk Factors Multiple pregnancy: risk >50% Previous preterm delivery: risk 20- 40% Cigarette smoking: risk 20-30% Cervical incompetence Uterine abnormalities MOH Sing. Guideline Grade C Recommendation 2001

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

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

3-Vaginal U/S Vaginal ultrasonography allows a more objective approach to examination of the cervix. Goldenberg , Obstetrics &Gynecology 11-2002

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. 2003 Apr;110 , 20:66-70. Meta-Analysis 40 studies

Prevention

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

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;97:149-54. Meta-anlysis of 6RCTs. Meis et al. N Engl J Med. 2003 Jun 12;348(24):2379-85.RCT (19 centers )

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. 2003 Mar 22;361:983-8. ) RCT

Diagnosis

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

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 11-2002

Treatment Inhibition of labor Corticosteroid Antibiotics Others.

Inhibition Of Labor Bed rest :DVT Hydration &sedation Tocolytics

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

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

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 1 2003. Oxford

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)

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 11-2002

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

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)

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

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 2005 unless otherwise indicated                                              

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. .

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 2002. In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.

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 2002. In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.

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)

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)

Indomethacin Indomethacin therapy for < 48 hours < 30-32 weeks' gestation) Not > 200mg/day. appears to be a relatively safe and effective tocolytic agent Goldenberg , Obstetrics &Gynecology 11-2002

Indomethacin Indomethacin can be used as a second-line tocolytic agent in early gestational age preterm labors. Goldenberg , Obstetrics &Gynecology 11-2002

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

Indomethacin 50 mg Loading dose Then 25-50mg /6hs Capsule 25mg oral Amp 50mg Rectal Supp 100 mg 50 mg Loading dose Then 25-50mg /6hs Newton eMedicine 2002

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

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)

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)

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) 9-2002. In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.

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)

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)

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

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

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

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 1 2003. Oxford: Update Software.

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

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 11-2002

Group B Streptococci (GBS) Prophylaxis The goal of this strategy is to prevent neonatal sepsis, and not to prevent preterm birth. Goldenberg , Obstetrics &Gynecology 11-2002

Prophylactic Vitamin K Or Phenobarbital Have not been shown to significantly prevent periventricular haemorrhages in preterm infants. Crowther & Henderson-Smart (Cochrane Review Novemb. 2000 ) In:The Cochrane Library, Issue 1 2003. Oxford: Update Software Crowther & Henderson-Smart (Cochrane Review May 2003 ) In:The Cochrane Library, Issue 1 2003. Oxford: Update Software Goldenberg , May 2003

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 .

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

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

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

Thank You