Management of Threatened Premature Labor

The choice of means to arrest premature labor is limited, as in majority of cases premature labor is associated with maternal and/or fetal complicating factors when the early expulsion of the fetus may be beneficial.

In cases when the fetus is not compromised, the maternal condition remains good and membranes are intact the following regimen may be administered to arrest premature labor.

Absolute bed rest is indicated, the patient should lie preferably on the left side.

In women with a singleton pregnancy, no history for preterm birth, and cervical length is 20 mm or less before or at 24 weeks vaginal progesterone 8% gel (90 mg daily) orMicronized progesterone capsules (200 mg vaginally daily) should be administered.

17 hydroxy progesterone caproate may be administered in dose 250 to 500 mg weekly by intramuscular injection during the first half of pregnancy.

Progesterone is a substance produced by the ovary and placenta that acts to prepare for and maintain pregnancy. Progesterone has been shown to help prevent the cervix from shortening in women with TPTL.

Tocolysis for preterm labor.Tocolysis is an inhibition of uterine contractions.

Tocolytic drugs may delay birth and allow: a). administration of corticosteroids; b). administration of Magnesium Sulfate for neuroprotection; c). in-utero transfer to an appropriate level facility.

There are contraindications for tocolysis:

- Acute fetal distress

- Chorioamnionitis

- Eclampsia or severe preeclampsia

- Fetal demise (singleton)

- Fetal maturity

- Maternal hemodynamic instability (eg, bleeding)

Indications for tocolysis:

- TPTL with intact amniotic membranes,

- cervical dilation < 4 cm,

- cervical effacement less than 80%.

Medications used as tocolysis:

- Ritodrine (Yutopar), Terbutaline (Bricanil) - β₂-adrenergic receptor agonists sympatomimetis, decrease free intracellular calcium ions.

- Magnesium sulphate -intracellular calcium antagonist.

- Indomethacin (Indocin) - prostaglandin inhibitor.

- Nifedipine (Epilate) - Calcium channel blocker.

- Atosiban (Tractocile) - inhibitor of the hormones oxytocin and vasopressin.

- Etanol

Ritodrine or Yutopar regimens:Ritodrine Hydrochloride may be prepared for intravenous infusion by dilution of 150 mg in 500 mL of 5% Dextrose to produce a solution containing 300 mcg (0.3 mg) of ritodrine hydrochloride per mL. Initial dose: IV, 50 to 100 mcg (0.05 to 0.1 mg) per minute, increased every ten minutes as necessary in increments of 50 mcg (0.05 mg) to the effective dose that balances uterine response and unwanted effects (increased maternal heart rate and decreased blood pressure and increased fetal heart rate), or until the maternal heart rate reaches 130 beats per minute. Maintenance: IV, 150 to 350 mcg (0.15 to 0.35 mg) per minute at the lowest dose that maintains a relaxed uterus.

Ritodrin (Yutopar) orally for tocolysis: start oral therapy 30 minutes before termination of IV infusion at 10 mg every 2 hours for 24 hours. Subsequently, 10-20 mg every 4-6 hours according to patient's response. Max oral dose 120 mg daily.

Bricanil / Terbutaline regimens: 1 ml solution for injection contains 0.5mg of terbutaline sulfate.

If a syringe pump is available, the concentration of the drug infused should be 0.1 mg/ml (10 ml Bricanyl Injection should be added to 40 ml of 5% dextrose). At this dilution:

5 mcg/min ≡ 0.05 ml/min and

10 mcg/min ≡ 0.1 ml/min

If no syringe pump is available, the concentration of the drug should be 0.01 mg/ml (10 ml Bricanyl Injection should be added to 490 ml of 5% dextrose. At this dilution:

5 mcg/min ≡ 0.5 ml/min and 10 mcg/min ≡ 1 ml/min.

Initially, 5 mcg/min should be infused during the first 20 minutes increasing by 2.5 mcg/min at 20 minute intervals until the contractions stop. More than 10 mcg/min should seldom be given, 20 mcg/min should not be exceeded. The dose must be individually titrated with reference to suppression of contractions, increase in pulse rate and changes in blood pressure, which are limiting factors. These parameters should be carefully monitored during treatment. A maximum maternal heart rate of 120 beats per min should not be exceeded. The infusion should be stopped if labor progresses despite treatment at the maximum dose. If successful, the infusion should continue for 1 hour at the chosen rate and then be decreased by 2.5 mcg/min every 20 minutes to the lowest dose that produces suppression of contractions.

Calcium antagonists (verapamil, finoptin, isoptin) in doses of 40-80 mg should be given 25 min before the beginning of infusion of b-adrenergic sympathomimetics to prevent side-effects of adrenomimetics to the heart system (maternal tachycardia). After infusion the same drug should be prescribed in tablets to prolong the effect. Usually 3 to 5 infusions are prescribed for treatment, one infusion daily.

Magnesium Sulfate regimen:Loading dose:IV MgSO₄ 4g bolus over 10-15 minutes (16 ml of 25% solution MgSO4 + 34 ml of normal saline solution)

Maintenance infusionof 1 g/h for at least 24 hours after the last convulsion (30 ml of 25% MgSO4 + 220 ml of normal saline solution with the rate 10-11 Dpm).

Indomethacin regimen: The initial recommended dose is 100 mg PR followed by 50 mg PO every 6 hours for 8 doses.

Nifedipine regimen: A recommended initial dosage of nifedipine is 20 mg orally, followed by 20 mg orally after 30 minutes. If contractions persist, therapy can be continued with 20 mg orally every 3-8 hours for 48-72 hours with a maximum dose of 160 mg/d. After 72 hours, if maintenance is still required, long-acting nifedipine 30-60 mg daily can be used.
Atosiban regimen:Each vial of 0.9 ml solution contains 6.75 mg atosiban (as acetate). Atosiban is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), performed with atosiban 6.75 mg/0.9 ml solution for injection, immediately followed by a continuous high dose infusion (loading infusion 300 micrograms/min) of atosiban 37.5 mg/5 ml concentrate for solution for infusion during three hours, followed by a lower dose of atosiban 37.5 mg/5 ml concentrate for solution for infusion (subsequent infusion 100 micrograms/min) up to 45 hours. The duration of the treatment should not exceed 48 hours. The total dose given during a full course of atosiban therapy should preferably not exceed 330.75 mg of atosiban.

Spasmolytics: papaverine hydrochloride, no-spa, actovegin, etc.are also used for tyreatment of TPTL

Glucocorticoid therapy is mandatory for patients with TPTL. Maternal administration of glucocorticoids is indicated at pregnancy term less than 34 weeks. This leads to fetal lung maturation so that the incidence of respiratory distress syndrome can be minimized. This is beneficial only when the delivery is delayed beyond 24 hours but less than 7 days. Treatment regimens include betamethasone, in a dosage of 12 mg given intramuscularly every 24 hours for two days, or dexamethasone, in a dosage of 6 mg given intramuscularly every 12 hours for two days.

In women with a singleton pregnancy, with a history of preterm birth at less than 34 weeks, already receiving progesterone since 16 weeks cervical cerclage should be considered if the cervical length is less than 25 mm before 24 weeks. Most often, isthmico-cervical incompetence is an indication for cervical cerclage during pregnancy.

Isthmico-cervical incompetence. Cervical insufficiency has no consistent definition, but is usually characterized by dilatation and shortening of the cervix before the 37th week of gestation in the absence of preterm labor, and is most classically associated with painless, progressive dilatation of the uterine cervix in the second or early third trimester resulting in membrane prolapse, premature rupture of the membranes, mid-trimester pregnancy loss, or preterm birth.

Cervical insufficiency arises from the woman’s inability to support a full-term pregnancy due to a functional or structural defect of the cervix. The classic history that raises the suspicion of cervical insufficiency is that of recurrent mid-trimester pregnancy losses. Congenital and acquired cervical abnormalities are causes of cervical insufficiency. Acquired risk factors (cervical trauma) are more common.

Cervical trauma may occur during previous childbirth (spontaneous, forceps- or vacuum-assisted delivery), rapid mechanical cervical dilation during gynecologic procedure (eg, uterine scraping), or treatment of cervical intraepithelial neoplasia. Congenital abnormalities include genetic disorders affecting collagen (eg, Ehlers-Danlos syndrome), uterine anomalies, in utero diethylstilbestrol (DES) exposure, and biologic variation.
Depending on the state, several types of cerclage are distinguished.

History-indicated cerclage: insertion of a cerclage as a result of factors in a woman’s obstetric or gynaecological history which increase the risk of spontaneous second-trimester loss or preterm delivery. A history-indicated suture is performed as a prophylactic measure in asymptomatic women and normally inserted electively at 12–14 weeks of gestation.

Ultrasound-indicated cerclage: insertion of a cerclage as a therapeutic measure in cases of cervical length shortening seen on transvaginal ultrasound. Ultrasound-indicated cerclage is performed on asymptomatic women who do not have exposed fetal membranes in the vagina.

Rescue cerclage: insertion of cerclage as a salvage measure in the case of premature cervical dilatation with exposed fetal membranes in the vagina. This may be discovered by ultrasound examination of the cervix or as a result of a speculum/physical examination performed for symptoms such as vaginal discharge, bleeding or ‘sensation of pressure’.

During pregnancy different types of operations may be recommended:

McDonald cerclage, Shirodcar’s suturing of the cervix, Scendy’s operation, Lubimova’s operation and others (Fig. 170, 171, 172).

The McDonald cerclage (Fig. 170) is the most commonly performed and recommended technique. It involves placing a purse-string suture through the cervix as close as possible to the internal os. Care should be taken to avoid the vessels at the 3 and 9 o'clock positions on the cervix. Permanent suture material, such as Mersilene tape or nylon, is used. A second stitch may be placed above the first. The knot usually is tied anteriorly to facilitate removal. The cerclage is removed at the time of labor, in the event of premature rupture of membranes, if infection is suspected, or at 37 weeks.

Fig. 170. MacDonald’s operation

2. In the Shirodkar cerclage (Fig. 171), the suture is buried beneath the cervical mucosa, after the bladder is dissected off the anterior cervix. The suture may be left permanently in place, which necessitates cesarean section for delivery, or may be removed to allow for a vaginal delivery. This type of cerclage is associated with more blood loss during placement than the McDonald cerclage and has not been proven to be more effective.

In cases in which a McDonald or Shirodkar cerclage has failed, an abdominal cerclage may be performed before the next pregnancy. Delivery via cesarean section is required after placement of this type of cerclage.

Fig. 171. The diagram of Shirodcar’s operation

3. The Lubimova’s operation (Fig. 172) is the most commonly used in our country. It involves placing of double U-shaped sutures through the cervix in the area of intenal os for constriction of the isthmic site. Lavsan or nylon material is usually used for suturing. The cerclage is removed at the time near the labor, usually at 36-37 weeks of gestation.

After the operation an absolute bed regimen should be prescribed for the patient for a few days, and then she must be under a special care of gynecologist till 36 weeks of gestation. Follow-up of the patient with a cerclage includes frequent cervical examinations either digitally or with ultrasonography. A reduced activity or bed rest as well as abstinence from sexual intercourse may be considered. At 36 week of gestation the sutures are usually taken off and spontaneous delivering will follow.

Fig. 172. The diagram of Lubimova’s operation

Other option of treatment of isthmico-cervical incompetence is plastic surgery of the cervix (Emmet’s operation) (Fig. 173), which should be done before the next pregnancy.

Fig. 173.The diagram of Emmet’s operation