Post on 31-Dec-2015
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?
Prediction1. Assessment of risk factors
2. Vaginal examination to assess the cervical status
3. Ultrasound visualization of cervical length and dilatation
4. 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
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
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
Other Risk Factors1-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
Other Risk Factors
1-Risk Factors
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
Outcome Sensitivity specificity
Delivery <37
Delivery <34
52%
53%
85%
89%
Delivery within 1 Week
Delivery within 2 Week
Delivery within 3 Week
Leitich & Kaider ,BJOG. 2003 Apr;110 , 20:66-70. Meta-Analysis 40 studies
71%
67%
59% 92%
89%
89%
4-Fibronectin Test
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.
Meis et al. N Engl J Med. 2003 Jun 12;348(24):2379-85.RCT (19 centers )
Keirse. Br J Obstet Gynaecol 1990;97:149-54. Meta-anlysis of 6RCTs.
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
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%.
Diagnosis
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
Nifedipine = Epilate
Atosiban= Tractocile
B –Sympathomimetic (Ritodrine)
Magnesium sulphate
Indomethacin
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
• 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 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.
Magnesium Sulfate
Nitric Oxide DonorsThere 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 Capsule 25mg oral
Amp 50mg
Rectal Supp 100 mg
Newton eMedicine 2002
50 mg Loading dose
Then 25-50mg /6hs
Atosiban: TractocilAtosiban, a synthetic
peptide, is a competitive antagonist of oxytocin at
uterine oxytocin receptors.
Atosiban: TractocilAtosiban - 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)
NifedipineNifedipine- 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)
NifedipineWhen 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
formulationsKing et al, (Cochrane Review) 9-2002. In: The Cochrane Library, Issue 1 2003. Oxford: Update Software.
Nifedipine20mg 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)
CorticosteroidsAntenatal 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
CorticosteroidsTwo 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.
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.
Goldenberg , May 2003
Crowther & Henderson-Smart (Cochrane Review May 2003 ) In:The Cochrane Library, Issue 1 2003. Oxford: Update Software
Crowther & Henderson-Smart (Cochrane Review Novemb. 2000 ) In:The Cochrane Library, Issue 1 2003. Oxford: Update Software
ConclusionsVarious 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 .
ConclusionsIf a tocolytic drug is
used, ritodrine no longer
seems the best choice.
ConclusionsOther 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
ConclusionsMaintenance tocolytic therapy has no proven effect.
It cannot be recommended for routine practice.
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