Common Mood Stabilizing Drug Can Increase Risk of Birth Defects

Lithium in the first trimester of pregnancy can affect the health of an unborn child, but doctors say stopping this medication can also be risky.

Babies of mothers who take lithium in the first trimester of pregnancy are at higher risk of major congenital malformations.

But not as high as researchers expected.

According to scientists from the Icahn School of Medicine at Mount Sinai in New York, that’s because previous studies looked at smaller groups.

In the largest study ever conducted to examine the risk of birth defects in babies exposed to lithium, the researchers used a meta-analysis of data from 727 lithium-exposed pregnancies.

They compared them to a control group of 21,397 pregnancies in mothers with mood disorders.

Those women weren’t taking lithium.

The researchers included data from Canada, Denmark, the Netherlands, Sweden, the United Kingdom, and the United States.

Among the babies not exposed to lithium in the first trimester, 4 percent were born with major malformations such has heart defects.

In babies exposed to lithium in the first trimester, the rate was 7 percent.

The study is published in The Lancet Psychiatry.

Hospital readmissions and other issues

The researchers also looked at neonatal hospital readmissions.

That risk was nearly twice as high for babies exposed to lithium (27 percent) compared to those who weren’t (14 percent).

No association was found between lithium and pregnancy complications.

These include such problems as preeclampsia, preterm birth, low birth weight, and gestational diabetes.

“Women should be informed on malformation risk in first-trimester exposed infants, but also about very high relapse risks for mental illness both during pregnancy and during the postpartum period,” Dr. Veerle Bergink, the study’s senior author and a professor of psychiatry and obstetrics, gynecology, and reproductive science at the Icahn School of Medicine at Mount Sinai, said in a news release.

She went on to say, “Given the well-documented effectiveness of lithium in reducing relapse in the perinatal period, some important clinical considerations are either to continue lithium in a lower dose during the first trimester or to restart lithium after the first trimester or immediately postpartum.”

Lithium and pregnancy

Lithium is a mood stabilizer used to treat bipolar disorder, which affects about 2 percent of the population.

Dr. Alex Dimitriu, a psychiatrist practicing in California, told Healthline that lithium is also used to increase the antidepressant benefit in people with depression who don’t fully respond to antidepressants.

Dimitriu explained that the risks of exposure to lithium are greatest in the first trimester.

“Although safer in the second and third trimesters, mothers who choose to remain on lithium should be monitored for normal thyroid function,” he said.

“Being on full doses of lithium around the time of delivery also has the potential to cause some sedation in newborns, which can manifest as lower muscle tone, sleepiness, and decreased feeding,” continued Dimitriu.

He noted that exposure to lithium in utero has been shown to have no impact on physical, mental, or behavioral issues later in life.

Dimitriu said that once the mother stops taking the drug, it’s cleared from the body in three to four days. It may take up to 10 days in long-term users.

“While lithium may be the standard for bipolar depression, there are many alternatives present today, especially the newer generation antipsychotics which have lower risks of causing fetal malformations,” he said.

He also pointed out that certain anticonvulsants such as valproic acid (Depakote) and carbamazepine (Tegretol) should be avoided due to even more significant risks than lithium.

Dimitriu said there’s no evidence of an association between fetal malformations or anomalies with lithium use in fathers.

Weighing the risks

Dimitriu said that the greatest risk for relapse of bipolar disorder is the period around childbirth.

Pregnancy is generally a time of improved stability for most mood disorders, according to Dimitriu.

But episodes can still occur.

“Research has shown that untreated mood episodes in pregnancy can also carry significant risk to the baby and mother with respect to self-care, sleep, nutrition, and stress hormone levels,” said Dimitriu.

“Depending on the severity of one’s illness, the benefits of staying on medication may outweigh the risks,” he said.

“However, this discussion is best had with the treating psychiatrist. It will likely involve a review of the severity and frequency of prior episodes,” said Dimitriu.

Dr. G. Thomas Ruiz is lead OB-GYN at MemorialCare Orange Coast Medical Center in California.

He told Healthline that if you have a major psychiatric illness requiring these medications, you should work with your mental health professional and your obstetrician.

He said for a woman with relatively stable manic depression under psychiatric care, it would be ideal to wean off lithium prior to getting pregnant.

“Then, you keep a close eye on her and if it looks like she’s going into a bad manic phase, then get her on medication,” he said.

Ruiz explained that the fetus is less vulnerable by the second trimester.

“You want the fetus to do well, but you have to take care of the woman. If you pull a severe manic depressive person off lithium, you’re talking about a patient that can really do harm to themselves. So, there’s a balance of the patient hurting herself versus hurting the fetus,” said Ruiz.

“You want to make sure the disease process — like any other medical problem — is stable before attempting to get pregnant. It’s quite possible that if you’re super stable you can decrease the dose first. But you let the psychiatrist manage the dosage,” he continued.

Monitoring is a team effort

Ruiz advised that people on lithium see a perinatologist specializing in high-risk pregnancies.

“We can manage these patients as high risk. We kind of assume if you’re on these drugs you can get these problems,” said Ruiz.

“We’ll do everything we can to rule out developmental complications or side effects in the pregnancy. Our radar will be on high alert,” he said.

Ruiz calls it a team effort. The team consists of the OB-GYN, the psychiatrist, and the perinatologist.

But they need help.

“It takes close observations by friends and family to make sure the person is not tipping into a manic phase. The spouse is usually the first to recognize the patient is losing touch with reality when the disease is starting to show itself,” said Ruiz.

“They may see an impending episode before the patient or the physician. You have to watch closely because as soon as the hormones of pregnancy leave the body, they’re susceptible again,” he continued.

“Everyone has to be acutely aware of the signs. The support structure is an important part of care,” said Ruiz.

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