Preterm Labor: A Crash Course

Preterm labor is a very serious complication of pregnancy. Unfortunately, many women do not understand the signs of preterm labor. Early detection can help prevent premature birth and possibly enable you to carry your pregnancy to term or to give your baby a better chance of survival.

Signs of Preterm Labor      Call your caregiver if you have any of the following:

~Contractions or cramps, more than 5 in one hour

~Bright red blood from your vagina

~Swelling or puffiness of the face or hands, a sign of preeclampsia

~Pain during urination, possible urinary tract, bladder or kidney infection

~Sharp or prolonged pain in your stomach (preeclampsia signs)

~Acute or continuous vomiting (preeclampsia signs)

~Sudden gush of clear, watery fluid from your vagina

~Low, dull backache

~Intense pelvic pressure

Prevention of Preterm Labor

While not all cases of preterm labor can be prevented there are a lot of women who will have contractions that can be prevented by simple measures. Nutrition is key in prevent preterm labor.  Also keep very well hydrated. We definately see the preterm labor rates go up in the summer months. What happens with dehydration is that the blood volume decreases, therefore increasing the concentration of oxytocin (hormone that causes uterine contractions) to rise. Hydrating yourself will increase the blood volume.

Others things that you can do would be to pay attention to signs ond symptoms of infections (bladder, yeast, etc.) because they can also cause infections. Keeping all of your appointments with your practitioner and calling whenever you have questions or symptoms. A lot of women are afraid of "crying wolf," but it is much better to be incorrect than to be in preterm labor and not being treated.

Management of Preterm Labor

There are a lot of variables to managing preterm labor, both in medical options and in terms of what is going on with you and/or your baby. Here are some of the things that you may deal with when in preterm labor.

~Hydration (Oral or IV)

~Bedrest (Home or Hospital), usually left side lying  (see the bedrest article)

~Medications to stop labor (Magnesium sulfate, brethine, terbutaline, etc.)

~Medication to help prevent infection (More likely if your membranes have ruptured or if the contractions are caused by infection)

~Evaulation of your baby (Biophysical profile, non-stress or stress tests, amniotic fluid volume index (AFI), ultrasound, etc.)

~Medications to help your baby's lung develop more quickly (Usually if preterm birth in inevitable)

~Prepartion for preterm birth

The best key is always prevention and early detection. Make sure to ask your practitioner to discuss the signs and symptoms of preterm labor to you and your partner at your next visit.

Preterm Labor Drugs aka Tocolytics

Side Effects, Complications

"No perfect tocolytic drug exists. Their use is not without potential problems for the mother, fetus and neonate."

- Washington Clark Hill, M.D., Clinical Obstetrics and Gynecology, Vol. 38, No. 4, p. 725.

"Tocolysis is a treatment of desperation and has a high failure rate."

- Mattox, John H., Core Textbook of Obstetrics and Gynecology, 1998, St. Louis, Mosby-Year Book, Inc., p. 205.

Disclaimer:

I am not a physician. This site provides information based on the research I've done and my own. Please check with your midwife or doctor if you have questions about your medical care.

"We recommend abandoning magnesium sulfate for routine use as a tocolytic therapy," the authors write. "On the basis of the findings of this study and our recent literature review...we believe that the scientific support for tocolytic magnesium sulfate is tenuous and, accordingly, that its use in that setting should be restricted to the confines of controlled clinical trials."

Am J Obstet Gynecol. 2002;186:1111-1118

New Study Links Mag Sulfate to Deaths of Fetuses, Newborns

Large preterm labor doses associated with a 4-fold increase in death risk

A retrospective review was done of fetal and newborn deaths at Chicago Lying-in Hospital between 1986-1999 where the mothers had been exposed to magnesium sulfate for preterm labor. The University of Chicago researchers found that fetuses and newborns exposed through their mothers to a dose of more than 48 grams of mag sulfate had 4.7 times the likelihood of dying than those who were exposed to lower doses. The greatest risk group was fetuses and infants who weighed less than 1250 grams but more than 699 grams (roughly a range of 1.7 pounds to 2.75 pounds). The researchers said 48 grams translated to about a one-day exposure to mag sulfate.

The researchers controlled for birth weight, gestational age, year of delivery, receipt of betamethasone (steroid to mature baby's lungs), acute maternal disease and maternal race. The researchers reviewed the records of 40,896 infants born during the studied time frame and found 207 whose mothers had received mag sulfate for preterm labor. Women who received mag sulfate for pre-eclampsia were excluded, as were fetuses and newborns with major congenital anomalies.

Source: Scudiero, Rebecca, et al., "Perinatal Death and Tocolytic Magnesium Sulfate," Obstetrics and Gynecology 2000, Vol. 96, pp. 178-182.

Reviews of PTL Drugs Find Few Benefits

Two reviews of all of the available preterm labor drugs in the U.S. conclude that most of these drugs are of limited or no value and that they pose significant risks to the health of women and their fetuses.

"Controversies in Tocolytic Therapy, " By Vern L. Katz and Richard M. Farmer (Clinical Obstetrics and Gynecology, 1999, Vol. 42, No. 4, pp. 802-819) concludes:

~Preterm labor drugs only treat the symptoms of the condition rather than the cause.

~Terbutaline and other drugs in its class (known as beta-adrenergics, beta-agonists or beta-mimetics) have cardiovascular and metabolic side effects and only temporarily halt preterm labor (for about 48 hours). They do not work in long-term use.

~Because of the serious side effects of terbutaline and the other beta-adrenergics, magnesium sulfate should be used as the first choice in preterm labor drugs.

~Indomethacin shows promise in short-term use, but has some serious fetal side effects when used over longer periods of time.

~Nifedipine shows some promise and fewer side effects than other preterm labor drugs. However it has not been well studied.

~Careful guidelines for the use of preterm labor drugs should be followed. These include: "The risk/benefit ratio for both mother and fetus must be re-evaluated on a continuing basis;" "Long-term use of tocolytics is difficult to justify at this time," and, "The safest tocolytic should be used for the shortest amount of time possible."

"A Risk-Benefit Assessment of Therapies for Premature Labour," by Kenneth Higby and Cheryl R. Suiter (Drug Safety 1999, July; 21 (1) pp. 35-56) concludes:

~Indomethacin, and other prostaglandin inhibitors like it, appear to work for short periods of time for women at less than 32 weeks gestation.

~Nifedipine (aka Procardia), and calcium antagonists like it, show promise but cannot be recommended because of insufficient studies.

~Atosiban, and other oxytocin antagonists like it, show promise but cannot be recommended because of insufficient studies.

~Magnesium sulfate is ineffective and the potential of adverse side effects is great. Its use as a preterm labor drug should be discontinued.

~Terbutaline, and other beta-agonists like it, work for a period of 24 to 48 hours. Long-term use has not been proven beneficial to mother or fetus. These drugs "have not been shown to decrease perinatal morbidity or mortality. Furthermore, mother and fetus are placed at substantial risk because of the high incidence of serious, often life-threatening, adverse effects."

Father of terb pump publishes new study

Despite FDA warning on pump, retrospective study compares it to pills

Dr. Fung Lam, who pioneered the use of the terbutaline pump, has published a new study (Journal of Perinatology 2000, Vol. 20, pp. 408-413). The study retrospectively examined the records of women who had been pregnant with twins and had received terbutaline pills for preterm labor and then had later been switched to the terbutaline pump. The study compared the lengths of time that these women received each form of terbutaline and found that women were on the pump longer before another episode of preterm labor and or delivery. The study says the average "pregnancy prolongation" was 19.3 days plus or minus 15.3 for women taking terbutaline pills and 34 days plus or minus 19.8 days for women on the terbutaline pump.

The study fails to mention at any point that the FDA warned doctors in 1997 that the terbutaline pump was neither safe nor effective. The FDA reaffirmed its position on the terbutaline pump in 1999. The study also does not mention any side effects associated with terbutaline. Carrying twins can put women at greater risk of side effects from preterm labor drugs.

The study authors state they did not use a double-blind placebo-control, which is considered the gold standard for research. A 1998 study that did use a double-blind trial found the terbutaline pump works no better than a placebo. The authors say the study was not designed to test the safety or effectiveness of terbutaline as maintenance therapy for preterm labor.

The study also seeks to compare two forms of terbutaline delivered to the same women at different points in their pregnancies. Most studies that compare different forms of a drug, administer them at the same time to different groups of women and conduct the comparison on that basis.

What side effects can I expect from terbutaline?

The most common side effects are:

~jitteriness

~increased heart rate

~tremors

Most of the other side effects are less common. If you experience any of these symptoms, you should contact your doctor promptly. If your doctor does not respond to your reports of adverse side effects, consider seeking a second opinion. Also, because of the risks of terbutaline, you should be screened carefully for any pre-existing health conditions.

Mild adverse effects

~Headache, dizziness, drowsiness, restlessness, insomnia (infrequent)

~Rapid, pounding heartbeat; increased sweating; muscle cramps in arms and legs (infrequent to frequent)

~Nausea, heartburn, vomiting (rare with oral form, frequent with IV)

~Increased blood sugar (frequent- 40% abnormal one-hour glucose test)

Serious adverse effects

~Rapid or irregular heart rhythm, intensification of angina, increased blood pressure (infrequent)

~Lowered blood calcium or potassium (especially with intravenous use) (possible)

~Liver toxicity (case reports)

~Severe lowering of blood pressure (hypotension) (case reports)

~Increased blood sugar (infrequent)

~Seizures (rare reports)

Effects of overdosage

~Nervousness, palpitation, rapid heart rate, sweating, headache, tremor, vomiting, chest pain

Sources: Rybacki, James, and Long, James, The Essential Guide to Prescription Drugs, New York: 1998, pp. 915-916.    1999 Physicians' Desk Reference, 52nd Ed., Montvale, NJ, pp. 1306-1307.

Terbutaline's side effects are more severe at higher dosages. As a reference point, the maximum dose of oral terbutaline for asthmatics is 15 mg per 24-hour period (The Essential Guide to Prescription Drugs, 1998 and 1999 Physicians' Desk Reference). However, women experiencing preterm labor will take terbutaline around-the-clock and often in significantly higher doses. At a dose of 5 mg every six hours, a woman is taking a total of 20 mg per 24 hour period, or 33% more than this maximum dose for asthmatics. At 5 mg every 4 hours, she is taking 30 mg per 24-hour period, or double the maximum dose for asthmatics. Sometimes the dosages of terbutaline for preterm labor can be even higher than 30 mg.

Some of terbutaline's more serious side effects include cardiovascular complications. These symptoms include:

~Dizziness or blackout

~Heart palpitations

~Tachycardia (rapid heart rate)*

~Irregular heart rate

~Frequent skipping of a heartbeat

~Chest pain

~Shortness of breath

Severe anxiety or restlessness

Source : Adapted from article by Roger B. Newman, M.D. Director, Maternal-Fetal Medicine, Medical University of South Carolina, on the Triplet Connection Web Page.

~Terbutaline and magnesium sulfate are not FDA-approved for use as preterm labor drugs. They are used "off label" for this purpose. In fact, virtually every drug used for preterm labor is used "off label" since Ritodrine's manufacturer took it off the market. Ritodrine was FDA-approved for preterm labor.

~At least 10 studies since the early 1980s reveal that terbutaline works no better than a placebo or no treatment in prolonging pregnancies after a period of 24-48 hours.

~Despite its use since 1969, few placebo-controlled or controlled studies have been done on whether magnesium sulfate actually works. The two published studies that used a placebo control or no treatment found that it worked no better than a placebo.

~Nifedipine (aka Procardia) is thought to be better tolerated than terbutaline and mag sulfate. In comparisons with Ritodrine (a sister drug of terbutaline), nifedipine worked better with fewer side effects. However, its long-term use has not been well studied and in a 1999 study it failed to prolong pregnancies any better than no treatment at all after contractions were stopped with magnesium sulfate.

~Terbutaline, an asthma drug, has been associated with some serious side effects/complications in pregnant women. These include chest pain, fast heart rate, arrythmias, peripartum cardiomyopathy, low blood sugar, low potassium levels, elevated liver enzymes and deaths.

~Magnesium sulfate is given in such high doses for preterm labor that the line between an "effective" and toxic dose is quite thin. An overdose of magnesium sulfate can be fatal to the mother. Meanwhile, two studies link its use to deaths of fetuses and newborn babies. The latest study from 2000 says the risk is especially great when high doses are used (greater than 48 grams) and the fetus/baby is tiny (about 1.7 to 2.7 lbs). The risk of death is 4.7 greater in these high doses than in doses less than 48 grams.  Combining preterm labor drugs can be dangerous.

~Very little research has been done on the long-term effects on children whose mothers took terbutaline while they were pregnant.

High doses of steroids (such as betamethasone) have been successfully used to mature the lungs of babies before delivery when their mothers experience preterm labor. However, studies were only done using one course of steroids. No studies have assessed the safety or efficacy of using multiple courses of steroids, which can be common when a woman is far from term. A study in Israel found women receiving multiple courses of steroids were more likely to suffer infections, some of them life-threatening.

Do Corticosteroids (Steroids) Pose Any Risks?

Safety of multiple doses is untested

High doses of corticosteroids like Betamethasone often are given by injection to pregnant women experiencing preterm labor or who have pre-eclampsia and may need to be delivered early. Controlled studies have shown that a single course (two 12 mg shots with a long lasting agent) of corticosteroids helps mature the baby's lungs and reduces the incidence of respiratory distress syndrome (RDS). RDS can be a fatal condition in preemies. Steroids also lessen the risk of intraventricular hemorrhage, another life-threatening preemie complication. In 1994, the National Institutes of Health endorsed the use of these steroids for cases of threatened preterm labor between 24 and 34 weeks gestation. The risks to pregnant women who take these steroids were lightly discussed. The severity of the potential complications was not addressed. For example, steroids often are given in combination with preterm labor drugs. The risk of a life-threatening complication called pulmonary edema increases when steroids and terbutaline are used together. Other studies have found an increased incidence of gestational diabetes among women who take the steroid-terbutaline combination. Still other studies, not mentioned by the NIH, have linked the combination of steroids and terbutaline (and other beta-adrenergics like it) to cardiovascular complications. Furthermore, the NIH made a blanket recommendation that steroids be used for all fetuses between 24 and 34 weeks gestation when preterm labor occurs. However, there were several areas of uncertainty when this recommendation was made. These areas include:

1.  Do steroids work in multiple gestations? The evidence is mixed, but some studies show steroids *do not* prevent RDS in multiple gestations. In fact, in one study involving women pregnant with triplets or quadruplets, the administration of steroids increased the chances that the women would go into labor. In addition, women pregnant with multiples face a higher risk of complications from steroids and preterm labor drugs.

2. Are multiple courses of steroids safe and effective? Most of the controlled studies were done with a single course (2 shots) of steroids. The protective effect of these shots are supposed to last about 7 days. However, women who go into preterm labor early in their pregnancy may receive many weeks of these shots. The safety of these repeated courses has not established, according to NIH's Consensus Statement. A retrospective1999 study found that women exposed to multiple courses of steroids had more infectious diseases than those women who did not (64.8% vs. 17.5%). Some of these infections were serious and potentially life-threatening. They included sepsis and pneumonia. The study authors say high doses of steroids are known to make patients more vulnerable to life-threatening bacterial, viral, fungal and parasitic agents. A high dose was defined as more than the equivalent of 10 mg of prednisone a day or 700 mg per week. Because of the long-lasting component in the betamethasone pregnant women receive, their equivalent dose in prednistone is 60-80 mg per day and a maximum cumulative dose of 3600-4200 mg of prednistone. This is just for *one course* of betamethasone. Women who receive many weeks of betamethasone shots obviously are exposed to even higher levels of these steroids.

Another retrospective study that compared multiple (greater than 2) to single courses of steroids in found that multiple courses of steroids were associated with a reduction in birth head circumference in preterm infants. Multiple courses of steroids also were associated with an increased incidence of endometritis (inflamation of the lining of the uterus) in the women who took them. Despite these side effects, the multiple course of steroids was associated with a lower incidence of RDS (35%) than the single course (45%).

References

"Effect of Corticosteroids for Fetal Maturity on Perinatal Outcomes," NIH Consensus Statement, Vol. 12, No. 2, February 28-March 2, 1994.

Abbasi, Soraya, et al., "Effect of Single versus Multiple Courses of Antenatal Corticosteroids on Maternal and Neonatal Outcome," American J. of Obstetrics and Gynecology 2000, Vol. 182, pp. 1243-9.

Elliott, John P. And Radin, Tari, "The Effect of Corticosteroid Administration on Uterine Activity and Preterm Labor in High-Order Multiple Gestations, " Obstetrics and Gynecology 1995, Vol. 85, pp. 250-4.

Fisher, Jay E. et al., "Gestational Diabetes Mellitus in Women Receiving Beta-Adrenergics and Corticosteroids for Threatened Preterm Delivery," Obstetrics and Gynecology 1997, Vol. 90, pp. 880-3.

Quist-Therson, Emmanuel C., et al., "Antenatal Steroids to Prevent Respiratory Distress Syndrome: Multiple Gestation as an Effect Modifier," Acta Obstet Gynecol Scan 1999, Vol. 78, pp. 388-392.

Rotmensch, Siegfried, et al., "Maternal Infectious Morbidity Following Multiple Courses of Betamethasone," Journal of Infection, 1999, Vol. 39, pp. 49-54.