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The prevalence of psychotropic drug use during pregnancy is high across all drug classes, but benzodiazepine use is particularly high. Benzodiazepines are used to treat anxiety and insomnia during pregnancy as well as pregnancy-associated nausea.

Use of these drugs during pregnancy has persisted, despite concerns regarding possible fetal risks that date back to the early 1970s. Concerns were raised that benzodiazepine use during the first trimester may increase the risk for major congenital malformations, specifically cleft lip and! or cleft palate (oral clefts). But subsequent studies found no increase in overall risk for major congenital malformations associated with benzodiazepines as a class of drugs.

There have been lingering concerns about a possible increased risk of oral clefts associated with first-trimester benzodiazepine exposure. Two recent metaanalyses assessed as a class various benzodiazepines such as lorazepam (Ativan), alprazolam (Xanax), diazepam (Valium), and clonazepam (Klonopin). The results suggested that the relative risk of oral clefts with first-trimester exposure may be raised but by no more than 0.6%.

The first metaanalysis combined studies that varied by quality, patient populations, and benzodiazepines used. The results suggested that the risk was increased by 0.6% with first-trimester exposure (Am. J. Psychiatry, 153[5]:592-606, 1996).

A more recent metaanalysis found no significantly increased risk of major malformations or oral clefts associated with first-trimester exposure to benzodiazepines in the cohort studies analyzed, although the case-control studies did show an increased risk for major malformations or oral clefts (BMJ 317[7162]:839-43, 1998).

At our center, we do not consider benzodiazepines as absolutely contraindicated during pregnancy, particularly for treatment of anxiety disorders. Untreated anxiety during pregnancy may be associated with compromised perinatal outcomes, such as preterm labor and lower APGAR scores. These outcomes may be secondary to the direct effect of untreated anxiety on the fetal-placental unit. It has been hypothesized that anxiety during pregnancy may be associated with fetal-placental insufficiency or uteroplacental insufficiency.

There have been anecdotal reports of benzodiazepine discontinuation syndromes in children born to mothers treated with high doses of benzodiazepines during pregnancy But the incidence of neonatal complications linked to benzodiazepine use during pregnancy in all probability is extremely small. In a study of 38 pregnant women with histories of panic disorder who were treated with 0.5-3.5 mg of clonazepam during pregnancy we found no evidence of neonatal toxicity or withdrawal syndromes in their babies (Psychother. Psychosom. In press).

Given the low incidence of perinatal complications associated with benzodiazepine use during labor and delivery or at term, it would seem apparent that abrupt discontinuation, particularly around delivery, is contraindicated. But physicians often discontinue these drugs arbitrarily either during pregnancy or during the peripartum period, without a sound basis for doing so.

Typically women with anxiety disorders have discontinued benzodiazepines during pregnancy because of concerns over oral clefts or perinatal toxicity. But we do not arbitrarily discontinue benzodiazepines during pregnancy or during the peripartum period.

Discontinuation of antipanic drugs during pregnancy appears to be associated with a high risk of relapse, which may be tied to compromised perinatal outcome. Several years ago, for example, we reported on a case of abruptio placentae associated with increases in blood pressure in a pregnant woman whose panic attacks were left untreated. And discontinuing treatment right before delivery increases a woman's risk of worsening anxiety disorders during that period.

A few reports have suggested that older children (followed up through age 5) whose mothers used benzodiazepines during pregnancy had some developmental delays, but these reports have been confounded by a history of substance abuse in their mothers. There are no other long-term behavioral data regarding the sequelae of benzodiazepine use during pregnancy.

Like other psychiatric drugs, benzodiazepines are secreted into breast milk but in most cases, the degree of exposure in the nursing infant is small and does not justify counseling a woman to defer breast-feeding. This is consistent with the American Academy of Pediatrics 2000 guidelines, which also advise against deferring treatment with benzodiazepines in this setting. We have reported on the use of benzodiazepines during lactation without difficulties or problems for the newborn.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston.
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Author:Cohen, Dr. Lee
Publication:OB GYN News
Date:Dec 1, 2000
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