Correspondence
The Control of Labor
N Engl J Med 1999; 341:2098-2099December 30, 1999
- Article
To the Editor:
In their review of the mechanisms that control labor (Aug. 26 issue),1 Norwitz et al. assert that magnesium sulfate is both safe and efficacious for the management of preterm labor. They also state that it has become the first-line treatment for preterm labor in North America. We were surprised by this unqualified endorsement of the usefulness of magnesium sulfate. A review of the scientific evidence has led us2,3 and others4-6 to different conclusions.
Although many obstetricians have had the anecdotal impression that delivery is delayed among patients undergoing tocolysis with magnesium sulfate, such an effect has never been proved in a rigorous way. In the only well-designed randomized clinical trial of the tocolytic efficacy of single-agent therapy with intravenous magnesium sulfate, as compared with saline control, Cox and associates found no difference in any measure of therapeutic effect.6 Similarly, in a recent systematic review of the literature, Kierse and coauthors concluded that “although magnesium sulphate may be efficacious for arresting uterine contractions in women who are not actually in preterm labor, its place in established preterm labor has not been demonstrated and it can have serious side-effects.”4
The statements by Norwitz and associates regarding the safety of tocolytic magnesium sulfate are equally controversial, with supportive data lacking.2-4 Stating that magnesium sulfate is safe and effective as a means of tocolysis (without citing supportive references) may mislead clinicians into thinking that such conclusions are firmly established.
6 ReferencesPeter G. Pryde, M.D.
University of Wisconsin Medical School, Madison, WI 53715Robert Mittendorf, M.D., Dr.P.H.
University of Chicago Pritzker School of Medicine, Chicago, IL 606371
Norwitz ER ,Robinson JN ,Challis JRG . The control of labor. N Engl J Med 1999;341:660-666
Full Text | Web of Science | Medline2
Mittendorf R ,Pryde PG ,Khoshnood B ,Lee KS . If tocolytic magnesium sulfate is associated with excess total pediatric mortality, what is its impact? Obstet Gynecol 1998;92:308-311
CrossRef | Web of Science | Medline3
Mittendorf R ,Covert R ,Boman J ,Khoshnood B ,Lee KS ,Siegler M . Is tocolytic magnesium sulphate associated with increased total paediatric mortality? Lancet 1997;350:1517-1518
CrossRef | Web of Science | Medline4
Kierse MJNC, Grant A, King JF. Preterm labor. In: Enkin M, Kierse MJNC, Renfrew MJ, Neilson JP, eds. A guide to effective care in pregnancy and childbirth. Oxford, England: Oxford University Press, 1998:161-73.
5
Bennett P ,Edwards D . Use of magnesium sulphate in obstetrics. Lancet 1997;350:1491-1491
CrossRef | Web of Science | Medline6
Cox SM ,Sherman ML ,Leveno KJ . Randomized investigation of magnesium sulfate for the prevention of preterm birth. Am J Obstet Gynecol 1990;163:767-772
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Drs. Pryde and Mittendorf express concern about the efficacy and safety of tocolytic magnesium sulfate and question the statement that magnesium sulfate has become the first-line treatment for preterm labor in North America. Nowhere in the review did we conclude that magnesium sulfate was effective in arresting preterm labor. Indeed, we specifically stated, “Although a number of [tocolytic] agents are now available . . . there are no reliable data to suggest that any of them delay delivery for more than 48 hours.”1
Since no single tocolytic agent has a clear therapeutic advantage, the decision about which of the available agents to use is often determined by the side effects of the drugs. Although no drug is without risk, there is considerable evidence to suggest that magnesium sulfate has fewer serious maternal and fetal side effects than the other available first-line tocolytic agents.2,3 Furthermore, there is mounting evidence to suggest that prenatal exposure to magnesium sulfate may reduce the risk of cerebral palsy and mental retardation in premature neonates. This potential reduction in risk is not due to selective mortality among infants exposed to magnesium sulfate and is independent of the putative tocolytic benefit of the drug.4
It is generally accepted, and Mittendorf and Pryde themselves have stated, with colleagues, that “magnesium [sulfate] ranks among the most popular tocolytics in the United States.”5 To address this issue, a questionnaire was recently sent to the directors of all 72 fellowship programs in maternal–fetal medicine in the United States that were identified by the Society for Maternal–Fetal Medicine. The response rate was 86 percent (62 of 72 questionnaires were returned). Magnesium sulfate was the reported first-line tocolytic agent in 85 percent of the responding institutions (53 of 62) (Ecker J, Greenberg J: personal communication).
In summary, although no perfect tocolytic drug exists, magnesium sulfate probably offers the most favorable benefit-to-risk ratio of all the available first-line tocolytic agents. The first rule of tocolysis is to use it only when indicated (i.e., in a patient with confirmed preterm labor before 34 weeks' gestation) and, as in all of medical practice, to tailor management to the individual patient.
5 ReferencesErrol R. Norwitz, M.D., Ph.D.
Julian N. Robinson, M.D.
Harvard Medical School, Boston, MA 021151
Norwitz ER ,Robinson JN ,Challis JRG . The control of labor. N Engl J Med 1999;341:660-666
Full Text | Web of Science | Medline2
Beall MH ,Edgar BW ,Paul RH ,Smith-Wallace T . A comparison of ritodrine, terbutaline, and magnesium sulfate for the suppression of preterm labor. Am J Obstet Gynecol 1985;153:854-859
Web of Science | Medline3
Hollander DI ,Nagey DA ,Pupkin MJ . Magnesium sulfate and ritodrine hydrochloride: a randomized comparison. Am J Obstet Gynecol 1987;156:631-637
Web of Science | Medline4
Schendel DE ,Berg CJ ,Yeargin-Allsopp M ,Boyle CA ,Decoufle P . Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years. JAMA 1996;276:1805-1810
CrossRef | Web of Science | Medline5
Mittendorf R ,Pryde PG ,Khoshnood B ,Lee KS . If tocolytic magnesium sulfate is associated with excess total pediatric mortality, what is its impact? Obstet Gynecol 1998;92:308-311
CrossRef | Web of Science | Medline
