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Recent Advances In Management
Of Preterm Labour

Dr. Hany Elkallaf
Assistant Professor OB& GYN
Faculty Of Medicine
Benha University
Defenition
Preterm labor is defined as the presence of contractions
of sufficient strength and frequency to effect
progressive effacement and dilatation of the cervix
between 20 and 37 weeks’ gestation
(American College of Obstetricians and Gynecologists, 2003)
Incidence
• Overall incidence of PTL : 6 % - 10 %
• Spontaneous

: 40 – 50 %

• PROM

: 25 – 40 %

• Obstetrically indicated

: 20 – 25 %

(Slattery and Morrison 2002 )
Risk Factors
I-Maternal factors :
• Previous preterm delivery .
• Low socioeconomic status .
• Maternal age <18 years or >40 years .
• Preterm premature rupture of the membranes .
• Multiple gestation .
• second-trimester abortions .
• Maternal complications (medical or obstetric) .
• Lack of prenatal care .
(Murphy.2007)
• Smoking.
Risk Factors
II-Uterine causes :
• Myomata (particularly submucosal or
subplacental) .
• Uterine septum .
• Bicornuate uterus .
• Cervical incompetence .
III-Fetal causes :
• Intrauterine fetal death .
• Intrauterine growth retardation .
• Congenital anomalies .
IV-Placental causes :
(Murphy.2007)
• Abnormal placentation
Risk Factors
V- Infectious factors :
•

Genital :
* Bacterial vaginosis (BV)
* Group B streptococcus

•

* Chlamydia
* Mycoplasmas

Intra-uterine :
* Ascending (from genital tract)
* Transplacental (blood-borne)
* Transfallopian (intraperitoneal)
* Iatrogenic (invasive procedures)

•

Extra-uterine :
* Pyelonephritis
* Typhoid fever
* Listeria

* Malaria
* Pneumonia
* Asymptomatic bacteriuria
(Jane Norman.2005)
Prediction of preterm labor
1. Risk factors .
2. Home uterine activity monitoring (HUAM) .
3. Cervical ultrasonography (Cx. Length assessment) .
4. Salivary estriol .
5. Screening for bacterial vaginosis (BV) .
6. Screening for fetal fibronectin (fFN) .
( Edwin and Sabaratnam. 2005)
Fetal fibronectin testing
• Sample :
from the posterior fornix of the vagina
• Indications:
1- Symptomatic preterm labour 24 - 36 weeks
2- Intact membranes and
3- Cervical dilatation less than 3 cm
• Contraindications:
1- Ruptured membranes
2- Vaginal bleeding
3- Cervical cerclage insitu
• Relative Contraindications:
1- After the use of lubricants or disinfectants
2- Within 24 hours of coitus or vaginal examination
(The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 2008)
Prevention of premature labor
• Primary prevention :
Aim :
lower the prevalence of premature labor by improving
maternal health in general and by avoiding risk factors before
or during pregnancy
Measures :
1- Smoking cessation .
2- Nutritional counseling .
3- lower workload for women with stressful jobs
( Flood and Malone ,2012 )

•
Prevention of premature labor
• Secondary prevention :
Aim :
Early identification of pregnant women at a risk of preterm labor
and helped them to carry their pregnancies to term.
Measures :
1- Self-measurement of the vaginal pH for B.V. (Bitzer.,et al.2011)
2- Cervix length measurement by TVS . ( Crane and hutchens ,2008)
(The accepted cutoff value for cervix length is ≤ 25 before GW 24 )

3- Cerclage and complete closure of the birth canal (Berghella.,et al.2011 )
4- Progesterone supplementation . ( Romero.,etal.2012)
Assessment and management of
PTL

• Secondary prevention :
Aim :
Early identification of pregnant women at a risk of preterm
labor and helped them to carry their pregnancies to term.
Measures :
1- Self-measurement of the vaginal pH for B.V.
2- Cervix length measurement by TVS .
(The accepted cutoff value for cervix length is ≤ 25 before GW 24 )

3- Cerclage and complete closure of the birth canal
4- Progesterone supplementation
•

Queensland Maternity and Neonatal Clinical Guideline (2009)
•
Treatment of premature
labor
• Inhibition of uterine contractions with tocolysis
• Corticosteroids to induce fetal lung maturation
• Treatment of infection with antibiotics
• Bed rest and hospitalization.
(Schleußner.2013)
Tocolysis
• Aim of tocolysis :
Suppress uterine contractions and delay preterm delivery
to :
1-allow in-utero transfer to an appropriate level facility .
2-allow for the administration of corticosteroids.
(King .,et al.2003)

•
•
Tocolysis
Contraindications :
• Gestation > 34 weeks
• Labour is too advanced
• In utero fetal death
• Lethal fetal anomalies
• Suspected fetal compromise
• Placental abruption
• Suspected intra-uterine infection
• Maternal hypotension: BP < 90 mmHg systolic
Relative contraindications :
. Multiple pregnancy
• pre-eclampsia
. Rupture of membrane
• placenta praevia
(Di Renzo et al., 2007)
Tocolysis
Tocolytic drugs that are used in clinical practice
•
•
•
•
•
•

Calcium antagonists . ( Nifedipine )
Oxytocin-receptor antagonists . ( Atosiban )
Inhibitors of prostaglandin synthesis . ( Indomethacin )
NO donors . ( Nitroglycerin)
Betamimetics . ( Terbutaline & Ritodrine )
Magnesium sulfate . ( MgSO4 )
•

•
Tocolysis

Mechanisms of action of tocolytic drugs
(Schleußner 2013)
Calcium channel blockers
((Nifedipine
• Dosage and administration :
30 mg loading dose,|then 10–20 mg every 4–6 h.

• Contraindications :
. Cardiac disease .

. Renal disease .
. Maternal hypotension (< 90/50 mm Hg) .
. Avoid concomitant use with magnesium sulphate .

• Maternal side effects :
. Flushing, headache .
. Transient hypotension .

. Nausea .
. Transient tachycardia .

• Fetal and neonatal side effects :
. Sudden fetal death .

. Fetal distress .
(Conde et al.,2011)
Atosiban (Tractocile)
(Tractocile
•

Dosage and administration :
Initial bolus dose 6.75 mg over one minute, followed by an
Infusion of 18 mg/h for 3 h and then 6 mg/h for up to 45 h.

• Contraindications :
. None .

• Maternal side effects :
. Nausea .
. Allergic reaction .
. Headache .

• Fetal and neonatal side effects :
. None
( De Heus et al.,2009 )
Prostaglandin synthetase inhibitors
( Indomethacin (
• Dosage and administration :

loading dose of 50 mg rectally or 50-100 mg orally, then
25-50 mg orally every 6 hr × 48 hr.
• Contraindications :
. Renal or Hepatic impairment
• Maternal side effects :
. Nausea, heartburn gastritis
. Increased PPHge

. Renal impairment function
. Headache, dizziness

• Fetal and neonatal side effects :
. Constriction of ductus arterious
. Oligohydramnios,
. Hyperbilirubinemia,

. Pulmonaryhypertension
. Intraventricularhemorrhage
. Necrotizing enterocolitis
( Haas et al.,2009 )
Nitric oxide donors
• Dosage and administration :
10 mg patch for every 12 hr continuing until contraction
cease up to 48 hours
• Contraindications :
. Headache
• Maternal side effects :
. Headache .
. Hypotension .
• Fetal and neonatal side effects :
. Neonatal hypotension
( Smith et al.,2007 )
•
•
Betamimetics
•

Dosage and administration :
1-Terbutaline 0.25 mg subcutaneously every 20 min. to 3 hr .
2-Ritodrine initial dose of 50-100 μg/min i.v., increase 50 μg/min
every 10 min until contractions cease or side effects develop,
maximum dose = 350 μg/min

•

Contraindications :
. Uncontrolled thyroid desease, & diabetes mellitus
. Cardiac arrythmias
(Anotayanonth et al.,2010 )

•

Maternal side effects :
. Hypokalemia
. Pulmonary edema

•

Fetal and neonatal side effects :
. Tachycardia.
. Hyperinsulinemia

. Hyperglycemia
. Arrhythmias

. Hypotension
. Myocardial ischemia
. Hyperglycemia
Magnesium sulfate
•

Dosage and administration :
Loading dose: 4g MgSO4 as a SLOW BOLUS over 15-30 minutes
Maintenance dose: 1g/hr. for 24/hr.
( Stop infusion if: RR<12 ,Hypotension ,loss of Patellar reflexes & UOP<100ml in 4hours )

•

Contraindications :
1- Hypersensitivity .
2- Hypermagnesemia & Hypercalcemia .
3- Myocardial damage, Diabetic coma, Heart block .

•

Side effects :
Magnesium toxicity include :
1- Hypotension & Hypothermia .
2- Cardiac and Central nervous system depression
3- Respiratory paralysis .
( Overdose is treated with 10ml of 10% Calcium Gluconate i.v. over 10 minutes )
(Lowes 2013)
Take home message
• Fetal fibronectin is a promising predictive test.

(Honest et al.,2009)

but

it may have limited accuracy in predicting preterm birth
within 7 days for women with symptoms of preterm labour .
(Sanchez-Ramos et al.,2009)

• Ultrasound assessment of cervical length is also a promising
predictive test for symptomatic women . ( Crane and hutchens .2008)
•
•
Take home message
•

There is no indication in routine clinical practice for
continuing tocolytic therapy for more than 48 hours. Except in
some cases (e.g., placenta previa hemorrhage, amniotic sac
prolapse).

(Schleußner.2013)

• Using multiple tocolytic drugs associated with a higher risk of
adverse effects and should be avoided.

(De Heus et al.,2009)
Take home message
•

Atosiban and Nifedipine appear to have comparable
effectiveness in delaying delivery, with fewer adverse effects
than alternatives such as Ritodrine or Indomethacin.
(RCOG Green-top Guideline. 2011)

• Ritodrine and Atosiban are licensed in the UK. for the treatment
of threatened preterm labour. Although the use of Nifedipine for
preterm labour is an unlicensed indication, it has the advantages
of oral administration and a low price.

(British National Formulary)

•
Take home message
• FDA warns against magnesium sulfate injections to pregnant
women for more than 5-7 days to stop preterm labor, as this agent
can lead to hypocalcemia and bone abnormalities in the fetus.
(Lowes.2013)

• Antenatal corticosteroid therapy should be initiated between 24
and 34 weeks gestation to reduce fetal morbidity.
(Porto et al.,2011)
Take home message
• Routine administration of antibiotics in premature labor
without premature rupture of the membranes is not
recommended .because the rate of maternal infection is lower ,
but pregnancy is not prolonged, nor reduction of the neonatal
complications .

(Subramaniam et al.,2012)

• There is no evidence that bed rest actually lowers the rate of
preterm birth.

(Crowther and Han. 2012)
Thank you

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Recent Advances In Management Of Preterm Labour

  • 1. Recent Advances In Management Of Preterm Labour Dr. Hany Elkallaf Assistant Professor OB& GYN Faculty Of Medicine Benha University
  • 2. Defenition Preterm labor is defined as the presence of contractions of sufficient strength and frequency to effect progressive effacement and dilatation of the cervix between 20 and 37 weeks’ gestation (American College of Obstetricians and Gynecologists, 2003)
  • 3. Incidence • Overall incidence of PTL : 6 % - 10 % • Spontaneous : 40 – 50 % • PROM : 25 – 40 % • Obstetrically indicated : 20 – 25 % (Slattery and Morrison 2002 )
  • 4. Risk Factors I-Maternal factors : • Previous preterm delivery . • Low socioeconomic status . • Maternal age <18 years or >40 years . • Preterm premature rupture of the membranes . • Multiple gestation . • second-trimester abortions . • Maternal complications (medical or obstetric) . • Lack of prenatal care . (Murphy.2007) • Smoking.
  • 5. Risk Factors II-Uterine causes : • Myomata (particularly submucosal or subplacental) . • Uterine septum . • Bicornuate uterus . • Cervical incompetence . III-Fetal causes : • Intrauterine fetal death . • Intrauterine growth retardation . • Congenital anomalies . IV-Placental causes : (Murphy.2007) • Abnormal placentation
  • 6. Risk Factors V- Infectious factors : • Genital : * Bacterial vaginosis (BV) * Group B streptococcus • * Chlamydia * Mycoplasmas Intra-uterine : * Ascending (from genital tract) * Transplacental (blood-borne) * Transfallopian (intraperitoneal) * Iatrogenic (invasive procedures) • Extra-uterine : * Pyelonephritis * Typhoid fever * Listeria * Malaria * Pneumonia * Asymptomatic bacteriuria (Jane Norman.2005)
  • 7. Prediction of preterm labor 1. Risk factors . 2. Home uterine activity monitoring (HUAM) . 3. Cervical ultrasonography (Cx. Length assessment) . 4. Salivary estriol . 5. Screening for bacterial vaginosis (BV) . 6. Screening for fetal fibronectin (fFN) . ( Edwin and Sabaratnam. 2005)
  • 8. Fetal fibronectin testing • Sample : from the posterior fornix of the vagina • Indications: 1- Symptomatic preterm labour 24 - 36 weeks 2- Intact membranes and 3- Cervical dilatation less than 3 cm • Contraindications: 1- Ruptured membranes 2- Vaginal bleeding 3- Cervical cerclage insitu • Relative Contraindications: 1- After the use of lubricants or disinfectants 2- Within 24 hours of coitus or vaginal examination (The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 2008)
  • 9. Prevention of premature labor • Primary prevention : Aim : lower the prevalence of premature labor by improving maternal health in general and by avoiding risk factors before or during pregnancy Measures : 1- Smoking cessation . 2- Nutritional counseling . 3- lower workload for women with stressful jobs ( Flood and Malone ,2012 ) •
  • 10. Prevention of premature labor • Secondary prevention : Aim : Early identification of pregnant women at a risk of preterm labor and helped them to carry their pregnancies to term. Measures : 1- Self-measurement of the vaginal pH for B.V. (Bitzer.,et al.2011) 2- Cervix length measurement by TVS . ( Crane and hutchens ,2008) (The accepted cutoff value for cervix length is ≤ 25 before GW 24 ) 3- Cerclage and complete closure of the birth canal (Berghella.,et al.2011 ) 4- Progesterone supplementation . ( Romero.,etal.2012)
  • 11. Assessment and management of PTL • Secondary prevention : Aim : Early identification of pregnant women at a risk of preterm labor and helped them to carry their pregnancies to term. Measures : 1- Self-measurement of the vaginal pH for B.V. 2- Cervix length measurement by TVS . (The accepted cutoff value for cervix length is ≤ 25 before GW 24 ) 3- Cerclage and complete closure of the birth canal 4- Progesterone supplementation • Queensland Maternity and Neonatal Clinical Guideline (2009) •
  • 12. Treatment of premature labor • Inhibition of uterine contractions with tocolysis • Corticosteroids to induce fetal lung maturation • Treatment of infection with antibiotics • Bed rest and hospitalization. (Schleußner.2013)
  • 13. Tocolysis • Aim of tocolysis : Suppress uterine contractions and delay preterm delivery to : 1-allow in-utero transfer to an appropriate level facility . 2-allow for the administration of corticosteroids. (King .,et al.2003) • •
  • 14. Tocolysis Contraindications : • Gestation > 34 weeks • Labour is too advanced • In utero fetal death • Lethal fetal anomalies • Suspected fetal compromise • Placental abruption • Suspected intra-uterine infection • Maternal hypotension: BP < 90 mmHg systolic Relative contraindications : . Multiple pregnancy • pre-eclampsia . Rupture of membrane • placenta praevia (Di Renzo et al., 2007)
  • 15. Tocolysis Tocolytic drugs that are used in clinical practice • • • • • • Calcium antagonists . ( Nifedipine ) Oxytocin-receptor antagonists . ( Atosiban ) Inhibitors of prostaglandin synthesis . ( Indomethacin ) NO donors . ( Nitroglycerin) Betamimetics . ( Terbutaline & Ritodrine ) Magnesium sulfate . ( MgSO4 ) • •
  • 16. Tocolysis Mechanisms of action of tocolytic drugs (Schleußner 2013)
  • 17. Calcium channel blockers ((Nifedipine • Dosage and administration : 30 mg loading dose,|then 10–20 mg every 4–6 h. • Contraindications : . Cardiac disease . . Renal disease . . Maternal hypotension (< 90/50 mm Hg) . . Avoid concomitant use with magnesium sulphate . • Maternal side effects : . Flushing, headache . . Transient hypotension . . Nausea . . Transient tachycardia . • Fetal and neonatal side effects : . Sudden fetal death . . Fetal distress . (Conde et al.,2011)
  • 18. Atosiban (Tractocile) (Tractocile • Dosage and administration : Initial bolus dose 6.75 mg over one minute, followed by an Infusion of 18 mg/h for 3 h and then 6 mg/h for up to 45 h. • Contraindications : . None . • Maternal side effects : . Nausea . . Allergic reaction . . Headache . • Fetal and neonatal side effects : . None ( De Heus et al.,2009 )
  • 19. Prostaglandin synthetase inhibitors ( Indomethacin ( • Dosage and administration : loading dose of 50 mg rectally or 50-100 mg orally, then 25-50 mg orally every 6 hr × 48 hr. • Contraindications : . Renal or Hepatic impairment • Maternal side effects : . Nausea, heartburn gastritis . Increased PPHge . Renal impairment function . Headache, dizziness • Fetal and neonatal side effects : . Constriction of ductus arterious . Oligohydramnios, . Hyperbilirubinemia, . Pulmonaryhypertension . Intraventricularhemorrhage . Necrotizing enterocolitis ( Haas et al.,2009 )
  • 20. Nitric oxide donors • Dosage and administration : 10 mg patch for every 12 hr continuing until contraction cease up to 48 hours • Contraindications : . Headache • Maternal side effects : . Headache . . Hypotension . • Fetal and neonatal side effects : . Neonatal hypotension ( Smith et al.,2007 ) • •
  • 21. Betamimetics • Dosage and administration : 1-Terbutaline 0.25 mg subcutaneously every 20 min. to 3 hr . 2-Ritodrine initial dose of 50-100 μg/min i.v., increase 50 μg/min every 10 min until contractions cease or side effects develop, maximum dose = 350 μg/min • Contraindications : . Uncontrolled thyroid desease, & diabetes mellitus . Cardiac arrythmias (Anotayanonth et al.,2010 ) • Maternal side effects : . Hypokalemia . Pulmonary edema • Fetal and neonatal side effects : . Tachycardia. . Hyperinsulinemia . Hyperglycemia . Arrhythmias . Hypotension . Myocardial ischemia . Hyperglycemia
  • 22. Magnesium sulfate • Dosage and administration : Loading dose: 4g MgSO4 as a SLOW BOLUS over 15-30 minutes Maintenance dose: 1g/hr. for 24/hr. ( Stop infusion if: RR<12 ,Hypotension ,loss of Patellar reflexes & UOP<100ml in 4hours ) • Contraindications : 1- Hypersensitivity . 2- Hypermagnesemia & Hypercalcemia . 3- Myocardial damage, Diabetic coma, Heart block . • Side effects : Magnesium toxicity include : 1- Hypotension & Hypothermia . 2- Cardiac and Central nervous system depression 3- Respiratory paralysis . ( Overdose is treated with 10ml of 10% Calcium Gluconate i.v. over 10 minutes ) (Lowes 2013)
  • 23. Take home message • Fetal fibronectin is a promising predictive test. (Honest et al.,2009) but it may have limited accuracy in predicting preterm birth within 7 days for women with symptoms of preterm labour . (Sanchez-Ramos et al.,2009) • Ultrasound assessment of cervical length is also a promising predictive test for symptomatic women . ( Crane and hutchens .2008) • •
  • 24. Take home message • There is no indication in routine clinical practice for continuing tocolytic therapy for more than 48 hours. Except in some cases (e.g., placenta previa hemorrhage, amniotic sac prolapse). (Schleußner.2013) • Using multiple tocolytic drugs associated with a higher risk of adverse effects and should be avoided. (De Heus et al.,2009)
  • 25. Take home message • Atosiban and Nifedipine appear to have comparable effectiveness in delaying delivery, with fewer adverse effects than alternatives such as Ritodrine or Indomethacin. (RCOG Green-top Guideline. 2011) • Ritodrine and Atosiban are licensed in the UK. for the treatment of threatened preterm labour. Although the use of Nifedipine for preterm labour is an unlicensed indication, it has the advantages of oral administration and a low price. (British National Formulary) •
  • 26. Take home message • FDA warns against magnesium sulfate injections to pregnant women for more than 5-7 days to stop preterm labor, as this agent can lead to hypocalcemia and bone abnormalities in the fetus. (Lowes.2013) • Antenatal corticosteroid therapy should be initiated between 24 and 34 weeks gestation to reduce fetal morbidity. (Porto et al.,2011)
  • 27. Take home message • Routine administration of antibiotics in premature labor without premature rupture of the membranes is not recommended .because the rate of maternal infection is lower , but pregnancy is not prolonged, nor reduction of the neonatal complications . (Subramaniam et al.,2012) • There is no evidence that bed rest actually lowers the rate of preterm birth. (Crowther and Han. 2012)