The US Food and Drug Administration (FDA; Silver Spring, MD, USA) advise clinicians not to give pregnant women magnesium sulfate (MgSO4) for more than 5–7 days, as it may harm developing fetal bones.
The FDA decision was based on a review of 18 case reports in the agency's Adverse Event Reporting System; in these cases, women were given the drugs for an average of 9.6 weeks, for an average total dose of 3,700 mg over treatment period. Abnormalities resulting in their offspring included fractures of the long bones and ribs, which may have been caused by fetal hypermagnesemia and the resulting hypocalcemia.
The FDA also reviewed the epidemiologic evidence. In one study, significantly more bone anomalies were seen in newborns that had been exposed to MgSO4 for more than one week, compared with only three days of exposure. Another study found differences in levels of osteocalcin, magnesium, calcium, and phosphorus at birth in babies exposed for longer than a week. The abnormalities seen in neonates in both studies after MgSO4 exposure of more than 5–7 days included radiographic findings of radiolucent transverse metaphyseal bands of long bones such as the humerus.
The FDA will change the teratogenicity category of MgSO4 from Pregnancy category D, rather than A, and a warning that longer off-label administration for tocolysis can lead to low calcium levels and osteopenia or fractures in the baby will be added to the drug's labeling. The labeling will also be amended to stress that injectable MgSO4 is not indicated for prevention of preterm labor, that its efficacy and safety for this use have not been established, and that it should only be administered by trained healthcare professionals in well-equipped hospitals.
“Pregnant women should discuss with their healthcare professional the possibility of going into labor before term and the risks and benefits of any treatments that may be used,” stated the FDA advisory. “However, the long-term significance of these findings is not known because of inadequate follow-up, and it is unknown whether a shorter duration of treatment is associated with calcium and bone abnormalities in the neonate.”
MgSO4 is an inorganic salt containing magnesium, sulfur, and oxygen, and is the first-line anti-arrhythmic agent for torsades de pointes in cardiac arrest. It is also used as a bronchodilator in severe exacerbations of asthma, and to treat eclampsia in pregnant women. It delays labor by inhibiting uterine muscle contraction in the case of premature labor. A recent systematic review suggests that antenatal intravenous MgSO4 can also reduce the risk of cerebral palsy and gross motor dysfunction in preterm infants by on average 30%.
US Food and Drug Administration