Is morphine (opioid analgesic) safe during pregnancy?

From the Guidelines

Morphine can be used in pregnant women, but only in specific situations such as during labor or after surgery, and under close medical supervision, as recommended by the most recent guidelines 1. The use of morphine in pregnancy should be approached with caution, considering the potential risks to the fetus and the newborn, including neonatal withdrawal syndrome, respiratory depression, and possible developmental effects. According to the prospect guideline for elective caesarean section 1, intrathecal morphine 50–100 μg or diamorphine 300 μg can be added to spinal anaesthesia for postoperative pain management. However, it is essential to weigh the benefits against the risks and to use the lowest effective dose for the shortest duration possible.

When considering pain management in pregnant women, it is crucial to prioritize strategies that minimize systemic opioid utilization, as recommended by the guideline 1. Alternative treatments, such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), should be considered first, and morphine should only be prescribed when these options are inadequate. The guideline also suggests considering a single injection of local anaesthetic infiltration, continuous wound local anaesthetic infusion, and/or fascial plane blocks, if intrathecal morphine is not used 1.

In terms of specific situations where morphine may be necessary, the guidelines for intraoperative care in cesarean delivery 1 suggest that intrathecal morphine can provide improved postoperative analgesia, although the risk of side-effects increases with the dosage used. However, the optimal dose is not established, and shorter-acting opioids such as fentanyl and sufentanil may be considered as alternatives 1. Ultimately, the decision to use morphine in pregnant women should be made on a case-by-case basis, taking into account the individual's specific medical situation and stage of pregnancy, and under the guidance of a healthcare provider.

Key considerations for the use of morphine in pregnant women include:

• Using the lowest effective dose for the shortest duration possible
• Prioritizing alternative treatments, such as paracetamol and NSAIDs
• Considering the risks of neonatal withdrawal syndrome, respiratory depression, and possible developmental effects
• Weighing the benefits against the risks and making individualized recommendations based on the patient's specific medical situation and stage of pregnancy.

From the FDA Drug Label

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy Risk Summary: Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5. 4)] . There are no available data with morphine sulfate tablets in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see Human Data] In published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (HDD) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0. 4 times the HDD in the rabbit, growth retardation at 6 times the HDD in the rat, and axial skeletal fusion and cryptorchidism at 16 times the HDD in the mouse Administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3 to 4 times the HDD; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the HDD [see Animal Data] . Based on animal data, advise pregnant women of the potential risk to a fetus.

Morphine is not recommended for use in pregnant women, especially during and immediately prior to labor, due to the potential risks to the fetus, including:

• Neonatal opioid withdrawal syndrome
• Respiratory depression in neonates
• Neural tube defects and other birth defects observed in animal studies The use of morphine in pregnant women should be carefully considered, and alternative analgesics or techniques should be used when possible 2.

From the Research

Morphine Use in Pregnancy

• Morphine is a type of opioid analgesic that may be used in pregnancy, but its use should be carefully considered due to potential risks to the fetus 3, 4.
• Studies have shown that over 50% of analgesics, including opioids, are classified as category C or D in pregnancy, indicating potential risks to the fetus 3.
• The use of morphine in pregnancy may be necessary in certain situations, such as for pain management, but it should be used under close medical supervision 4, 5.
• Research has shown that morphine can be effective in inducing therapeutic rest in pregnant women, but it may also increase the risk of admission in labor 5.

Safety and Efficacy

• The safety and efficacy of morphine use in pregnancy have been studied, and results suggest that it may be associated with adverse outcomes, such as increased risk of admission in labor 5.
• However, other studies have found that morphine use in pregnancy may not be associated with significant differences in maternal or neonatal morbidity 5.
• The pharmacokinetics of morphine may be affected by pregnancy, and dose adjustments may be necessary to maintain therapeutic concentrations and minimize risks to the fetus 3.

Alternative Options

• Non-opioid analgesics, such as NSAIDs and acetaminophen, may be considered as alternative options for pain management in pregnancy 6, 7.
• These alternatives may be effective in managing acute pain, but they also carry risks and should be used under medical supervision 7.
• Combination therapy using a small amount of opioid with a non-opioid pain reliever may also be an effective option for managing acute pain in pregnancy 7.