Treatment recommendations

Guidelines

There are no specific guidelines for the treatment of pain in pregnancy. The choice of analgesic should be guided by recommendations for non-pregnant people taking into consideration the risks to the fetus.

Avoid using medicines in the first trimester wherever possible – the period of greatest susceptibility to teratogenic effects (i.e. malformations) is usually the first 12 weeks of pregnancy.

See our content on the principles of prescribing during pregnancy and pain: treatment during pregnancy. You should check to see if there is local guidance for you to use in your area.

Choose the most appropriate opioid

Conduct an individual assessment of the risk versus benefit for the use of medicines in pregnancy when looking at the available information and choosing the most appropriate opioid. Check to see if the specialist team has already completed a risk assessment.

Weak opioids

Weak opioids are codeine, dihydrocodeine and tramadol.

Consider weak opioids (with paracetamol) first for mild to moderate pain taking into account the risk to the fetus.

Strong opioids

Examples of strong opioids are morphine, buprenorphine, fentanyl and oxycodone.

Strong opioids may be required for more severe pain and may be considered after evaluating the risk of fetal adverse effects from in utero exposure. Their use needs to be reviewed regularly.

Potential complications

Maternal complications

Opioids may exacerbate constipation, nausea and vomiting, which may already be a problem in pregnant women.

Neonatal withdrawal

Complications from neonatal withdrawal may occur with the use of opioid analgesics in pregnancy. Use of any opioid during pregnancy, particularly if it has been used long-term and/or around the time of delivery, confers a risk of neonatal respiratory depression.

The neonatology team should be informed if pregnant women have been receiving long-term opioids.

Symptoms

Symptoms of neonatal withdrawal from opioids include:

• difficulty breathing
• extreme drowsiness (sleepiness)
• poor feeding
• irritability
• sweating
• tremors
• vomiting
• diarrhoea

These symptoms will most often appear two days after birth and may last more than two weeks.

Weak opioids

Codeine

Codeine has often been the weak opioid of choice in pregnancy because there are more data available regarding its use in human pregnancy compared to other weak opioids. The use of codeine at any stage in pregnancy would not usually warrant any additional fetal monitoring. If clinically indicated, codeine should be used at the lowest effective dose for the shortest possible duration.

However, codeine is not recommended for use during breastfeeding. The duration of treatment required may influence the choice of weak opioid used in pregnancy. See our content on using codeine, dihydrocodeine or tramadol during breastfeeding for more information.

It should be noted that codeine is metabolised to morphine.

Risk of malformations

Most data on the use of codeine in pregnancy (any trimester), whilst limited, do not suggest an increase in risk of fetal malformations. A possible association with respiratory and cardiac malformations has been reported following first trimester exposure to codeine.

UK Teratology Information Service (UKTIS) codeine monograph has more detailed information on pregnancy outcomes.

Neonatal respiratory depression

Using codeine (as with all opioid analgesics) near the end of the third trimester may cause neonatal respiratory depression and long-term use may cause neonatal withdrawal symptoms.

Dihydrocodeine

Dihydrocodeine has an analgesic efficacy similar to codeine. Higher doses may provide some additional pain relief compared with codeine, but this may be at the cost of more nausea and vomiting. The use of dihydrocodeine at any stage in pregnancy would not usually warrant any additional fetal monitoring. If clinically indicated, dihydrocodeine should be used at the lowest effective dose for the shortest possible duration.

Risk of malformations

There are no adequate data on the safety of dihydrocodeine in human pregnancy though it has been used without apparent adverse effects for several years. Any risks are expected to be similar to those for codeine.

UKTIS dihydrocodeine monograph has more detailed information on pregnancy outcomes.

Neonatal respiratory depression

The use of dihydrocodeine (as with all opioid analgesics) near the end of the third trimester may cause neonatal respiratory depression and long-term use may cause neonatal withdrawal symptoms.

Tramadol

Tramadol is used to treat moderate-to-severe pain. It produces analgesia via two mechanisms: an opioid effect and an enhancement of serotonergic and adrenergic pathways. It has fewer of the typical opioid side-effects (respiratory depression, constipation and addiction potential) though psychiatric reactions have been reported. The use of tramadol at any stage in pregnancy would not usually be considered as medical grounds for termination of pregnancy. If clinically indicated, tramadol should be used at the lowest effective dose for the shortest possible duration.

Risk of malformations

Most data regarding risks of congenital malformation following first trimester tramadol exposure, though limited, are reassuring.

Possible associations between first trimester exposure and infant cardiovascular defects and a foot defect called talipes equinovarus have been identified. However, these are not confirmed by larger studies.

UKTIS tramadol monograph has more detailed information on pregnancy outcomes.

Neonatal respiratory depression

The use of tramadol (as with all opioid analgesics) near the end of the third trimester may cause neonatal respiratory depression and long-term use may cause neonatal withdrawal symptoms.

Other complications

The largest and most methodologically robust study available does not indicate an increased risk of miscarriage following gestational tramadol exposure. A single cohort study found no increased risk of preterm delivery.

Strong opioids

Buprenorphine

Buprenorphine is a semi-synthetic opioid that only partially activates opiate receptors. The use of buprenorphine at any stage in pregnancy would not usually be considered as medical grounds for termination of pregnancy. Pregnancies complicated by severe pain may require additional fetal monitoring, this should be assessed on a case-by-case basis. If clinically indicated, buprenorphine should be used at the lowest effective dose for the shortest possible duration.

Risk of malformations

There are limited data on the use of buprenorphine in human pregnancies, which do not indicate associations with congenital malformations. However, data are too limited to fully exclude increased risks.

UKTIS buprenorphine monograph has more detailed information on pregnancy outcomes.

Neonatal respiratory depression

The use of buprenorphine (as with all opioid analgesics) near the end of the third trimester may cause neonatal respiratory depression and long-term use may cause neonatal withdrawal symptoms. Due to the long half-life of buprenorphine, neonatal monitoring for several days after birth should be considered.

Other complications

The available data on buprenorphine exposure in human pregnancy do not indicate associations with stillbirth, preterm delivery or low infant birth weight. However, data are too limited to fully exclude increased risks.

Fentanyl

Fentanyl is a very potent opioid analgesic and is available in a range of medicinal products including transdermal patches. The use of fentanyl at any stage in pregnancy would not usually be considered as medical grounds for termination of pregnancy. The need for additional fetal monitoring or prenatal investigations should be decided on a case-by-case basis. If clinically indicated, fentanyl should be used at the lowest effective dose for the shortest possible duration.

Risk of malformations

The safety of fentanyl in human pregnancy has not been established and the very limited data available are insufficient to assess the risk of teratogenicity.

UKTIS fentanyl monograph has more detailed information on pregnancy outcomes.

Neonatal respiratory depression

The use of fentanyl (as with all opioid analgesics) near the end of the third trimester may cause neonatal respiratory depression and long-term use may cause neonatal withdrawal symptoms.

Other complications

The limited data available do not currently raise concerns about other adverse pregnancy outcomes.

Morphine

Morphine remains the most used opioid analgesic for severe pain although it frequently causes nausea and vomiting.

RCOG guidance suggests that morphine can be taken during all stages of pregnancy at the lowest effective dose for the shortest possible duration.

Risk of malformations

There is no robust evidence of an increased malformation risk, a possible association with childhood strabismus (a visual defect) has been suggested. This association is not confirmed because the data for morphine use in human pregnancy are inadequate with conflicting studies that are often confounded by other factors.

UKTIS morphine monograph has more detailed information on pregnancy outcomes.

Neonatal respiratory depression

The use of morphine (as with all opioid analgesics) near the end of the third trimester may cause neonatal respiratory depression and long-term use may cause neonatal withdrawal symptoms.

Other complications

Some studies have suggested a possible association between morphine use in pregnancy with altered fetal growth in utero and an increased risk of preterm delivery. However, data are extremely limited in relation to low birth weight, preterm delivery, stillbirth and neurodevelopmental outcomes.

Oxycodone

Oxycodone has an efficacy and side-effect profile similar to that of morphine. It is commonly used as a second-line medication if morphine is not tolerated or does not control the pain. The use of oxycodone at any stage in pregnancy would not usually be considered as medical grounds for termination of pregnancy. If clinically indicated, oxycodone should be used at the lowest effective dose for the shortest possible duration.

Risk of malformations

There is no indication that the use of oxycodone in early pregnancy increases malformation rates, but the available data are insufficient to exclude an increase in risk.

UKTIS oxycodone monograph has more detailed information on pregnancy outcomes.

Neonatal respiratory depression

The use of oxycodone (as with all opioid analgesics) near the end of the third trimester may cause neonatal respiratory depression and long-term use may cause neonatal withdrawal symptoms.

Other complications

The UKTIS mentions one study of over 2,000 exposed pregnancies which found that oxycodone exposure in the first and second trimesters was associated with a small increased risk of preterm delivery (absolute risk ~10% vs. background risk ~7%).

Limitations

This page focusses on therapeutic use of opioids commonly used to treat pain in primary care and areas of secondary care that are not highly specialised.

We do not cover substitution use for opioid abuse in pregnancy or opioids used during labour.

Further information

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