Preterm Labor:

Evidence Based View

Dr.Mohamed El Sherbiny
MD Obstetrics&Gynecology
Senior Consultant
Damietta General Hospital
Damietta Egypt
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 .
 Risks were higher for those
screened at <16 weeks (odds ratio,
7.55; 95% CI, 1.80-31.65) than those
at <20 weeks of gestation (odds
ratio, 4.20; 95% CI, 2.11-8.39).
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

Delivery <37 52% 85%

Delivery <34 53% 89%

Delivery within 1 Week 71% 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
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

• 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
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.
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:TheGoldenberg
Cochrane Library, Issue 1 2003. Oxford: Update Software
, 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