Recent Advances In ManagementRecent Advances In Management Of Preterm Labour Of Preterm Labour

Dr. Hany ElkallafDr. Hany ElkallafAssistant Professor OB& GYN

Faculty Of MedicineBenha University

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)

DefenitionDefenition

IncidenceIncidence

• Overall incidence of PTL : 6 % - 10 %

• Spontaneous : 40 – 50 %

• PROM : 25 – 40 %

• Obstetrically indicated : 20 – 25 %

(Slattery and Morrison 2002 )

Risk FactorsRisk 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 .• Smoking. (Murphy.2007)

Risk FactorsRisk 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 :• Abnormal placentation (Murphy.2007)

Risk FactorsRisk FactorsV- Infectious factors :• Genital : * Bacterial vaginosis (BV) * Chlamydia * Group B streptococcus * Mycoplasmas

• Intra-uterine : * Ascending (from genital tract)

* Transplacental (blood-borne) * Transfallopian (intraperitoneal) * Iatrogenic (invasive procedures)

• Extra-uterine : * Pyelonephritis * Malaria

* Typhoid fever * Pneumonia * Listeria * Asymptomatic bacteriuria (Jane Norman.2005)

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Prediction of preterm laborPrediction 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)

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Fetal fibronectin testingFetal 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)

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Prevention of premature laborPrevention 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 )

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Prevention of premature laborPrevention 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)

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Assessment and management of PTLAssessment 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)•

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Treatment of premature Treatment of premature laborlabor

• Inhibition of uterine contractions with tocolysis

• Corticosteroids to induce fetal lung maturation

• Treatment of infection with antibiotics

• Bed rest and hospitalization. (Schleußner.2013)

TocolysisTocolysis

• 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)

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TocolysisTocolysis

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 : • pre-eclampsia . Multiple pregnancy• placenta praevia . Rupture of membrane (Di Renzo et al., 2007)

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TocolysisTocolysis

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 )

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TocolysisTocolysis

(Schleußner 2013)

Mechanisms of action of tocolytic drugs

Calcium channel blockers Calcium channel blockers ((NifedipineNifedipine))

• 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 . . Nausea . . Transient hypotension . . Transient tachycardia .• Fetal and neonatal side effects : . Sudden fetal death . . Fetal distress . (Conde et al.,2011)

Atosiban (TractocileAtosiban (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 inhibitorsProstaglandin synthetase inhibitors( Indomethacin )( 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 . Renal impairment function . Increased PPHge . Headache, dizziness

• Fetal and neonatal side effects : . Constriction of ductus arterious . Pulmonaryhypertension . Oligohydramnios, . Intraventricularhemorrhage . Hyperbilirubinemia, . Necrotizing enterocolitis ( Haas et al.,2009 )

Nitric oxide donoNitric oxide donorsrs

• 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 )

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BetamimeticsBetamimetics

• 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 . Hyperglycemia . Hypotension . Pulmonary edema . Arrhythmias . Myocardial ischemia

• Fetal and neonatal side effects : . Tachycardia. . Hyperinsulinemia . Hyperglycemia

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Magnesium Magnesium sulfatesulfate

• 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)

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Take home messageTake 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)

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Take home messageTake 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)

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Take home messageTake 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)

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Take home messageTake 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)

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Take home messageTake 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 youThank you