What are the effects of sedatives on pregnancy?

From the Guidelines

Sedatives should be avoided during pregnancy unless absolutely necessary due to potential risks to the developing fetus, and if required, the lowest effective dose should be used for the shortest duration possible, particularly avoiding the first trimester when possible. The use of sedatives during pregnancy is a concern due to the potential risks of birth defects, withdrawal symptoms in newborns, respiratory depression, and neurodevelopmental effects 1. Non-pharmacological approaches, such as relaxation techniques, cognitive behavioral therapy, and improved sleep hygiene, should be tried first. If medication is necessary, benzodiazepines like midazolam are preferred over other sedatives, but their use should be limited to short-term purposes and only when benefits clearly outweigh risks 1. It is essential for pregnant women to discuss all medications, including over-the-counter sleep aids, with their healthcare provider to develop an individualized plan that balances maternal health needs with fetal safety considerations. The FDA has also recommended caution with the use of benzodiazepine receptor agonistic modulators due to reports of disruptive sleep-related behaviors, and patients should be advised about the potential for these adverse effects 1.

Some key points to consider when using sedatives during pregnancy include:

• Avoiding the use of sedatives during the first trimester when possible
• Using the lowest effective dose for the shortest duration possible
• Preferring midazolam over other benzodiazepines for sedation
• Avoiding the combination of sedatives with alcohol, other sedatives, or sleep restriction
• Discussing all medications, including over-the-counter sleep aids, with a healthcare provider to develop an individualized plan
• Considering non-pharmacological approaches, such as relaxation techniques and cognitive behavioral therapy, before using medication.

From the FDA Drug Label

Advise pregnant females that use of diazepam late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal Diazepam has been shown to be teratogenic in mice and hamsters when given orally at daily doses of 100 mg/kg or greater (approximately eight times the maximum recommended human dose [MRHD=1 mg/kg/day] or greater on a mg/m 2basis) Cleft palate and encephalopathy are the most common and consistently reported malformations produced in these species by administration of high, maternally toxic doses of diazepam during organogenesis.

The effects of sedatives, specifically diazepam, on pregnancy include:

• Sedation in newborns, which can manifest as respiratory depression, lethargy, and hypotonia
• Withdrawal symptoms in newborns, such as hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties
• Teratogenic effects, including cleft palate and encephalopathy, when given at high doses during organogenesis 2 2 It is essential to monitor neonates exposed to diazepam during pregnancy and labor for signs of sedation, respiratory depression, hypotonia, and feeding problems, and to manage them accordingly.

From the Research

Effects of Sedatives on Pregnancy

• The use of sedatives, such as benzodiazepines, during pregnancy can have various effects on the fetus and the mother 3, 4.
• Studies have shown that some benzodiazepines, like diazepam, can be safe to use during pregnancy, but not during lactation, as they can cause lethargy, sedation, and weight loss in infants 3.
• Other benzodiazepines, such as alprazolam, should be avoided during pregnancy and lactation due to potential risks 3.
• The pharmacokinetic properties of benzodiazepines play a crucial role in their use during pregnancy, labor, and lactation, with rapid placental transfer and significant fetal uptake of the drug 4.
• High peak concentrations of benzodiazepines should be avoided, and the daily dosage should be divided into two or three doses to minimize risks 3.

Risks and Considerations

• The use of benzodiazepines during pregnancy may increase the risk of preterm birth, low birthweight, and small-for-gestational-age infants 5.
• There is a lack of randomized controlled trials and empiric evidence regarding the safety of prescribing sedatives during pregnancy, making it challenging for clinicians to make informed decisions 5.
• Managing benzodiazepine withdrawal during pregnancy poses unique challenges, and guidelines for detoxification during pregnancy are necessary 6.
• Insomnia during pregnancy is a common issue, and the use of sedatives, such as benzodiazepines, may be considered, but the risks and benefits must be carefully weighed 7.

Medication-Specific Considerations

• Diazepam can be safe to use during pregnancy, but not during lactation 3.
• Chlordiazepoxide may be safe to use during pregnancy and lactation 3.
• Alprazolam should be avoided during pregnancy and lactation 3.
• Oxazepam, lorazepam, nitrazepam, and flunitrazepam may penetrate the human placenta more slowly than diazepam, but the clinical significance of this phenomenon is uncertain 4.