Only two randomized studies have evaluated tocolysis with magnesium sulfate. Cotton and colleagues (1984) compared magnesium sulfate, ritodrine, and placebo in 54 women with preterm labor. They identified few diferences in outcomes. Cox and coworkers (1990) randomly assigned 156 women to receive magnesium sulfate or infusions of normal saline. Magnesium-treated women and their neonates had identical outcomes compared with those given placebo. Because of these findings, this method of tocolysis was abandoned at Parkland Hospital. Similarly, Crowther and associates (2014) reviewed magnesium sulfate as a tocolytic agent and concluded it was inefective and potentially harmful. Last, the FDA (2013) has warned against prolonged use of magnesium sulfate given to arrest preterm labor because of bone thinning and fractures in fetuses exposed for more than 5 to 7 days. This was attributed to low calcium levels in the fetus.
hese compounds are intimately involved in contractions of normal labor (Chap. 21, p. 416). Antagonists act by inhibiting prostaglandin synthesis or by blocking their action on target organs. A group of enzymes collectively termed prostaglandin synthase is responsible for the conversion of free arachidonic acid to prostaglandins. Several drugs block this system, including acetylsalicylate and indomethacin.
Indomethacin, a nonselective cyclooxygenase inhibitor, was first used as a tocolytic in one study of 50 women (Zuckerman, 1974). Studies that followed reported the eicacy of indomethacin in halting contractions and delaying preterm birth (Muench, 2003; Niebyl, 1980). Morales and coworkers (1989, 1993a), however, compared indomethacin with either ritodrine or magnesium sulfate and found no diference in their eicacy to forestall preterm delivery. Berghella and associates (2006) reviewed four trials of indomethacin given to women with a sonographically determined short cervix and found such therapy to be inefective.
Indomethacin is administered orally or rectally. Most studies have limited indomethacin use to 24 to 48 hours because of concerns for oligohydramnios, which can develop with therapeutic doses. If amnionic luid is monitored, oligohydramnios can be detected early, and it is reversible with drug discontinuation.
In a study of neonates born before 30 weeks, Norton and coworkers (1993) identiied necrotizing enterocolitis in 30 percent of 37 indomethacin-exposed newborns compared with 8 percent of 37 control newborns. Higher incidences of intraventricular hemorrhage and patent ductus arteriosus were also documented in the indomethacin group. Several investigators have challenged the association between indomethacin exposure and necrotizing enterocolitis (Muench, 2001; Parilla, 2000). Similarly, Gardner (1996) and Abbasi (2003) and their colleagues found no link between indomethacin use and intraventricular hemorrhage, patent ductus arteriosus, sepsis, necrotizing enterocolitis, or neonatal death. Two metaanalyses of the efects of antenatal indomethacin on neonatal outcomes had conflicting indings (Amin, 2007; Loe, 2005). Reinebrant and colleagues (2015) in a review of 20 studies reported no clear benefit from cyclooxygenase inhibitors, including indomethacin, compared with placebo or any other tocolytic agent.