Literature Review

Migraine Treatments Previously Deemed Safe During Pregnancy Could Pose Serious Risks



Migraine treatments such as magnesium, ondansetron, acetaminophen, and butalbital could be harmful if taken during pregnancy, according to a study published in the April issue of Current Neurology and Neuroscience Reports. Having a history of migraine could have serious effects on the health of a pregnancy and perinatal outcomes, making safe and effective treatment important. “Patients and doctors need to be aware that concerns exist and they should carefully weigh the risks and benefits of these treatments,” said Rebecca Erwin Wells, MD, MPH, Assistant Professor of Neurology at Wake Forest Baptist Health in Winston-Salem, North Carolina, and colleagues.

Rebecca Erwin Wells, MD, MPH


Magnesium was formerly considered the only safe supplement for migraine during pregnancy, but its safety was recently challenged by the FDA. Eighteen case reports in the FDA’s Adverse Event Reporting System raised new concerns about potential risks such as low calcium, bone abnormalities, and rickets-like skeletal abnormalities in neonates exposed to IV magnesium in utero. Magnesium sulfate is still indicated for prevention and control of seizures in pre-eclampsia and eclampsia, however. The FDA reclassified magnesium sulfate injection as pregnancy category D because of its potential teratogenic effects. More research is needed to further understand the safety of magnesium in migraine prevention.


Ondansetron is a popular antiemetic treatment for pregnant mothers, but recent findings have raised new concerns about fetal and maternal safety. The FDA released warnings about the risk of serotonin syndrome and serious dysrhythmias that the drug entails. In an observational study, 176 pregnant women exposed to ondansetron were compared with those exposed to other antiemetics and nonteratogens. No increased risks of major malformations with ondansetron were found. A case–control study in 2012 found that ondansetron increased the risk of cleft palate in offspring. A Danish investigation involving 897,018 women who were pregnant between 1997 and 2010 revealed a doubling in the prevalence of cardiac malformations with ondansetron use, but the data were not statistically significant. In a report published in the New England Journal of Medicine, Danish researchers examined 609,385 pregnancies from 2004 to 2011 and found no increased risks of adverse fetal outcomes associated with ondansetron.


Acetaminophen has been considered one of the safest analgesics to use during pregnancy, and more than 65% of pregnant women in the United States use it. Recent evidence, however, suggests possible links between maternal acetaminophen use and pediatric development of attention deficit hyperactivity disorder (ADHD) and wheezing. A Danish National Birth Cohort study from 1996 to 2002 involving 64,322 live-born child and mother pairs indicated that acetaminophen use during pregnancy was associated with an increased risk of ADHD-like behavior, a diagnosis of hyperkinetic disorder, or ADHD medication use at seven years. The greatest risk was associated with use during multiple trimesters and for more than 20 weeks. The Norwegian Mother and Child Cohort Study (1999–2008) involved 2,919 same-sex sibling pairs of mothers who were evaluated for paracetamol exposure and psychomotor and behavior development. Children with more than 28 days of prenatal exposure to paracetamol had poorer gross motor development, communication, and externalizing/internalizing behavior and higher activity levels.

Another prospective study, however, reported no significant relationship between maternal acetaminophen use in the first half of pregnancy and child IQ or attention. Other studies have linked paracetamol exposure to an increased risk of pediatric wheezing and asthma. However, in an Italian prospective birth cohort study involving 3,538 children, researchers found that all such associations were explained by confounding factors such as age at delivery, smoking, siblings, and asthma or asthmatic bronchitis.


Butalbital has been considered an abortive treatment of choice for migraine during pregnancy. According to the National Birth Defects Prevention Study, however, butalbital is associated with a potential increase in congenital heart defects. In this study, which involved 21,090 infants exposed to butalbital and 8,373 unaffected controls, periconceptual butalbital use was linked to tetralogy of Fallot, pulmonary valve stenosis, and secundum-type atrial septum defect. The small sample size limited the study’s power.

Nonpharmacologic and Procedure-Based Treatments

Pregnant women who are concerned about the risks associated with magnesium, ondansetron, acetaminophen, butalbital, or other pharmacologic treatments can try nonpharmacologic treatments. Therapies such as relaxation training, biofeedback, and physical therapy can be helpful for treatment of migraines. Healthy habits such as having a balanced diet, avoiding alcohol, limiting caffeine consumption, staying properly hydrated, and getting adequate sleep and exercise can also aid in preventing migraines.

Procedure-based migraine treatment options include craniosacral therapy and acupuncture. Craniosacral therapy involves gentle maneuvers to address restrictions in the craniosacral system. Evidence for this treatment’s efficacy in migraine, however, is limited. Acupuncture is as effective as prophylactic drug treatment for preventing migraine, and could help minimize nausea and vomiting that accompany headaches. If migraines persist with nonpharmacologic treatments, other recommended pharmacologic options such as beta-blockers, tricyclic antidepressants, riboflavin, coenzyme Q10, and pyridoxine could be effective and safe treatments.

Next Article:

Self-Administered Tool Identifies Chronic Migraine

Related Articles