Organogenesis phase

There is theoretical reason to suspect that drugs used in anaesthesia may be teratogenic: the cellular mechanisms for differentiation and organogenesis include mechanisms known to be targeted by drugs used in anaesthesia. Neurotransmitter and receptor mechanisms, as well as signalling and second messenger systems are all known to be affected by drugs used in anaesthesia. This theoretical risk of teratogenicity has been difficult to quantify in a practical clinical context, because of difficulties extrapolating animal research data to human development (teratogenicity is species specific) and the obvious ethical and logistical problems of research on human fetal exposure to teratogens.

Later pregnancy

Drugs used in later pregnancy may have direct effects other than structural organogenesis impairment.

Benzodiazepines in late pregnancy may result in fetal benzodiazepine dependence and withdrawal (although unlikely in the short-term context of a single anaesthetic). Used peripartum, they are associated with fetal hypotonia, respiratory depression and hypothermia, and are probably best avoided in a viable gestation pregnancy.

Opioids have similar potential for fetal dependence and withdrawal, but again this is unlikely to result from short-term anaesthetic use. Peripartum opioid use results in reversible respiratory depression.

Non-steroidal anti-inflammatory drugs in the third trimester have been linked to premature closure of the ductus arteriosus, tricuspid incompetence and pulmonary hypertension. They have been associated with a range of fetal and neonatal effects consistent with their side-effect profile (including platelet dysfunction and intracranial haemorrhage, renal impairment and gastrointestinal bleeding), and their use should be avoided after 32 weeks’ gestation.

Neuromuscular blocking agents are polar molecules that do not readily cross the maternal–placental barrier and are safe to use in late pregnancy.

The antiemetic prochlorperazine has been associated with neonatal jaundice and extrapyramidal side effects when used in high dose late in pregnancy.

Organogenesis phase

There is some evidence that chronic hypercarbia and hyperthermia may be teratogenic, but it seems unlikely that anaesthesia would result in such exposure.

Later pregnancy

Derangements in maternal physiology that are precipitated or exacerbated by anaesthesia are likely to impact on the fetus by their effects on uteroplacental perfusion and oxygen delivery. Regardless of the cause of reduced uteroplacental perfusion, the fetal effects are similar: acidosis and fetal hypoxaemia will result. The insult may result in fetal injury, ranging from transient mild acidosis or hypoxaemia to brain injury, and ultimately to fetal death if the injury is unrecognized or untreated.