With Intact Membranes
There is no completely safe drug that will predictably and reliably turn off true preterm labor. Besides the uncertain value of the medications in stopping preterm labor, they all carry risks to the mother or the fetus or both. They must be used only with close observation. If a woman clearly has a vaginal or urinary tract infection, that condition is treated, although once labor has begun, antibiotic therapy will not stop it.
Without a known cause of preterm labor, treatment is aimed at stopping the contractions, rather than alleviating the cause. This is sometimes effective, although studies have shown that most treatments postpone birth for only 48 hours. This is enough time, however, to give the mother a medication that many experts believe speeds up maturation of the fetal lungs, helping to increase survival. It is also sufficient time to transfer the pregnant woman to a hospital that has a neonatal intensive care unit(NICU), called a tertiary care center or a Level III hospital. This is preferable to transferring a premature infant after birth, which poses more risks for the newborn and separates the mother and baby.
Promoting Fetal Lung Maturity: A corticosteroid drug called betamethasone or dexamethasone is given to the mother to promote fetal lung maturity. This drug is thought to cause the fetal lung to produce surfactant-a chemical that keeps the lungs expanded after each breath. In respiratory distress syndrome(previously called hyaline membrane disease), the lungs of the premature newborn collapse after each breath, making each breath as difficult as the first. This is a major cause of death in premature infants. Surfactant appears in the fetal lung in the second trimester, but may not be present in sufficient quantity to be effective before 34 weeks of pregnancy.
In 1995, the National Institutes of Health(NIH) hailed the use of corticosteroids as a major breakthrough in care for preterm newborns. Since this report, the therapy has been used widely in preterm labor. Recent studies, however, have not consistently supported its value.
For corticosteroids to be beneficial in causing lung maturity, there must be a delay of at least 24 hours between treatment and birth. If birth is delayed for 7 days, their effectiveness is unclear.
Standard regimens for administering the medication vary. One major obstetrical text reports the use of two doses of 12 mg betamethasone, injected into the muscle, 24 hours apart, or 12 hours apart if labor seems likely to occur before 48 hours have passed. Another major text reports use of 5 mg of dexamethasone every 12 hours for four doses. The therapy may be repeated every 7 days until 34 weeks gestation, although some controversy exists about whether repeated courses of steroid treatment might impair brain or immune system development in the fetus. More research is needed in this area.
Stopping Labor: Various drugs have been used to stop preterm labor, including beta-adrenergic receptor agonists, magnesium sulfate, prostaglandin inhibitors, calcium channel blocking agents, and oxytocin inhibitors. The act of stopping uterine contractions is called tocolysis(Greek: tocos = birth; lysis = dissolution). Women with medical diseases may not be able to use some or any of these drugs as they aggravate certain conditions.
Beta-Adrenergic Receptor Agonists. A group of cells called adrenergic receptors are found on the surface of smooth muscle cells. An agonist is a drug or other substance that can combine with the receptor cells. In the uterine muscle, stimulation of the beta-adrenergic receptors by an agonist causes the receptors to inhibit uterine contractions. Two beta-adrenergic agonists used to stop preterm contractions are ritodrine and terbutaline, although only ritodrine is approved for this use by the Food and Drug Administration.
Studies have found that these medications, given intravenously, stop labor for a day or two, at most. While this doesn’t give the fetus much time to grow, it may allow for the adminstration of corticosteroids or maternal transfer.
Since beta-adrenergic receptors are found in smooth muscle cells all over the body, these drugs affect many body systems. This limits their use. They can cause heart and lung problems, as serious as rapid or irregular heartbeat, decreased blood pressure, chest pain, and pulmonary edema(fluid in the lungs). They cause changes in body chemistry, including increased blood sugar, decreased blood potassium, and increased blood insulin levels. They cause less serious but quite unpleasant side effects such as vomiting, headaches, fever, and hallucinations. They may cause anxiety in the woman.
Women receiving ritodrine or terbutaline must be hospitalized and watched with extreme care. Women with poorly controlled diabetes or poorly controlled high blood pressure should not be given beta-adrenergic agonists.
Magnesium Sulfate. Another medication used in the effort to stop preterm labor is magnesium sulfate, usually given intravenously. Studies show its effects on labor to vary from none to stopping labor for the same duration as ritodrine. Magnesium can depress maternal respiration, although this effect is rare. A woman must be closely observed while the drug is being given. Magnesium therapy may also cause nausea and vomiting, decreased blood pressure, and headache. Magnesium eventually crosses the placenta and may affect newborn respirations as well.
Magnesium sulfate cannot be used in women with kidney failure, low blood calcium levels, or a disease called myasthenia gravis(characterized by severe muscle weakness).
Prostaglandin Inhibitors. Prostaglandins are a group of body chemicals involved in normal uterine contractions. Prostaglandins can be given to induce labor. Conversely, prostaglandin inhibitors can be used to stop labor. These inhibitors work by either reducing the formation of prostaglandins or blocking their action. Indomethacin is an example of a prostaglandin inhibitor that has been used to arrest labor.
Research studies have found prostaglandin inhibitors more effective than beta-agonists for delaying labor up to 48 hours, with fewer maternal side effects. Prostaglandin inhibitors, however, are associated with severe adverse effects on the fetus, including cardiac defects and brain hemorrhage. They can also cause bleeding in the mother. The use of these drugs for stopping labor is still under investigation.
Indomethacin cannot be used with maternal asthma, coronary artery disease, gastrointestinal bleeding, kidney failure, and oligohydramnios. Suspected heart or kidney abnormalities in the fetus also preclude its use.
Calcium Channel Blocking Agents. Reducing calcium levels in muscle cells reduces muscle contraction. Calcium channel blockers stop the entry of calcium into cells. (These drugs are used to treat high blood pressure because they relax the muscles in blood vessels.) An example of a calcium channel blocker that has been used to stop preterm labor is nifedipine.
Studies have shown that nifedipine can postpone delivery by 3 daysÂa greater delay than that seen with ritodrine. Maternal side effects are less than with ritodrine. The effect of this drug on the fetus, however, has not been studied extensively. Because it relaxes the muscles in blood vessels, it could lead to decreased blood pressure in the mother. This, in turn, could lead to decreased blood flow to the placenta. The extent to which this occurs warrants further study.
Nifedipine should not be used with magnesium sulfate as it enhances the effect of magnesium, leading to serious lung and heart problems. Women with liver disease cannot use nifedipine.
Oxytocin Inhibitors. Atosiban is a type of drug currently under development. It works by inhibiting oxytocin, a chemical responsible for uterine contractions. Its use has been limited but it may prove to be beneficial in the future.
The search for safer and more predictable drugs continues. It is difficult to slow down or speed up the uterus without affecting other body systems. The best drug would be one that limits its effects to the uterine muscle. Such a substance has not been identified.
Treatment of Premature Rupture of the Membranes
Premature rupture of the membranes(PROM) occurs as an uncontrollable gush or leakage of fluid. By definition, PROM is rupture of the membrane that occurs more than 12 hours before the onset of labor. If this occurs before 37 weeks gestation, it may be called preterm premature rupture o/the membranes(PPROM).
In the past, due to concern that prolonged rupture of membranes would lead to maternal and fetal infection, babies were all delivered shortly after rupture, regardless of gestational age. Research has not shown this to be beneficial to mother or baby.
Today, one of two care paths generally is followed when a woman has PPROM without labor:
1.
Nothing is done except to wait for labor with monitoring of maternal temperature and avoidance of all vaginal examinations.
2. Corticosteroid therapy is initiated, with or without medications to try to stop labor.
Delivery is only induced in the presence of maternal fever, indicating infection. Most women with PPROM will be in labor, either immediately or within 2 days.
Women with ruptured membranes before 37 weeks usually are admitted to the hospital for observation. The woman may be discharged home before the baby is born if the leakage of fluid stops and certain other conditions exist. The baby should be in the vertex or head down position; there must be no sign of infection; the woman must be able to rest and avoid vaginal intercourse at home; the woman or somebody in her family must be able to read a thermometer; the woman must be able to return for prenatal care visits at least weekly. This is a decision to be made individually for each woman.