General information on drug use in pregnancy: nonprescribed drugs

Introduction

Pregnancy may represent an opportunity for the clinician to discuss modification of maternal drinking and smoking behaviours. Every effort should be made to capitalise on a woman's motivation to enter treatment during this time.

Educational and behavioural interventions are the mainstay of treatment. Pharmacological treatments should be considered only after specialist consultation.

Alcohol

Ten to fifteen per cent of pregnant women continue to consume alcohol, despite its being a well-established teratogen. The effects of alcohol on the fetus tend to be lifelong, and are best conceptualised as lying along a continuum of severity known as the 'fetal alcohol spectrum disorders'. The severe neurotoxic effects of 'high' consumption (especially binge drinking) have been well documented for over 40 years, ie the fetal alcohol syndrome. The latter is characterised by growth retardation, intellectual handicap, neurological damage and characteristic craniofacial abnormality. This risk does not appear to be confined to first trimester consumption, and it is possible that the pattern of drinking may be more important than the average number of drinks per week. Neonatal withdrawal is also associated with heavy use in late pregnancy.

Controversy and ongoing debate continue regarding how much, if any, alcohol consumption is 'safe' during pregnancy. This is accompanied by efforts to define and detect the less severe presentations of the fetal alcohol spectrum disorders (ie those without facial abnormalities). Draft Australian guidelines have been made consistent with those of the US and most other Western countries in recommending total abstinence during pregnancy. This is based on human longitudinal studies suggesting permanent adverse impacts on children's behavioural and neurocognitive function at low levels of consumption (eg 1 to 2 standard drinks per week). Animal studies further support the potential for low intake to interfere with normal brain development. However, in human studies, numerous potential confounding variables (including psychosocial ones) render these longitudinal data difficult to interpret.

Alcohol has also been associated with increased risk of spontaneous abortion, premature delivery and stillbirth.

The safety of anticraving drugs such as naltrexone and acamprosate has yet to be established.

Nicotine

During pregnancy, approximately 23% of Australian women report having smoked. Such women often have higher prevalence of other risk factors (eg substance abuse, poor nutrition, noncompliance with antenatal care and a suboptimal living environment). Nevertheless, there is substantial evidence suggesting a causative link between smoking itself and several adverse outcomes. For many of these outcomes there appears to be a dose-dependent relationship with the number of cigarettes smoked. Mechanisms are less clear, but literature has highlighted the potential importance of other harmful ingredients in cigarette smoke, apart from nicotine. In particular, carbon monoxide is a powerful neuroteratogen, and can also induce fetal cellular hypoxia through formation of carboxyhaemoglobin. Fetal concentration of the latter has been shown to be 1.8 times maternal concentration.

The main adverse outcomes associated with smoking during pregnancy are:

It appears that up to 25% of Australian women smokers quit smoking without professional help when pregnancy is confirmed. However, this abstinence may not continue throughout the pregnancy, and the majority of these women resume smoking after delivery.

The available evidence suggests that, in pregnant women, counselling may exert more influence on smoking than pharmacological interventions. Nicotine replacement therapy (NRT) during pregnancy remains controversial, as nicotine itself has been linked to some of the above problems (excluding growth retardation, but including neurotoxicity) in animal studies. However, there is an emerging consensus that with NRT usage the level of nicotine exposure to the fetus is less than that in women who continue to smoke heavily. Moreover, cigarette smoke is known to contain a large number of other potentially harmful ingredients, and these are avoided in successful NRT. The latter can be regarded as a possible adjunct to counselling, especially in women smoking more than 10 cigarettes per day. However, usually it is not started unless a trial of psychological interventions has failed. If NRT is used, it should always be coupled with a psychological intervention, and care should be taken to ensure that the initial dose is minimised but consistent with the previous level of smoking (nicotine metabolism is more rapid in pregnancy). The woman should be warned that smoking while using NRT is potentially dangerous, especially in women predisposed to vasospasm. When commencing NRT, intermittent regimens (eg nicotine gum or lozenge) rather than continuous regimens (eg transdermal patch) are sometimes recommended. The latter can be introduced if intermittent replacement fails, and should be used for 16 rather than 24 hours. Whether replacement should be started in the first trimester is controversial following publication of a much-quoted longitudinal study suggesting a possible link to malformations. This study awaits replication, and had methodological weaknesses.

The safety of bupropion during pregnancy has yet to be established.

Caffeine

Studies suggest that the majority of pregnant women consume 100 to 300 mg of caffeine each day. Typical doses are around: 100 to 150 mg/150 mL for brewed coffee, 60 to 100 mg/150 mL for instant coffee and 30 to 100 mg/150 mL for tea. Cola drinks contain 35 mg/250 mL, caffeine tablets contain 100 to 200 mg and energy drinks average 80 mg/250 mL. [Note 1]

There is no evidence that moderate caffeine intake presents a teratogenic risk. However, caffeine consumption of greater than 200 mg per day has been linked to a significantly increased risk of spontaneous miscarriage. The available evidence also suggests that high intake (in excess of 300 mg per day), may increase the risk of preterm delivery, and foetal growth retardation. Whether lower intake also carries risk remains controversial.

There is no evidence of long-term neurobehavioural toxicity in children of women with moderate intake of caffeine in pregnancy.

Cannabis

In most developed countries, approximately 10% of women smoke cannabis at some point in pregnancy. Animal and human research suggests that permanent neurobehavioral effects can result, and the nature of these depends on the gestation at exposure. Longitudinal studies suggest that, compared to controls, such children may have cognitive (especially visuospatial) deficits, greater impulsivity and hyperactivity, more attention defects and higher rates of depression. Interpretation of these data require caution owing to a number of possible confounding factors.

Amphetamine and methamphetamine

Animal studies are strongly suggestive of the potential teratogenicity of amphetamine and methamphetamine. In humans, clefting and cardiac abnormalities have been described in case reports or small series. However, numerous possible confounding factors in drug-abusing women make these findings difficult to interpret.

More firmly established is the association between use of these substances during pregnancy and fetal growth retardation (smaller head circumference, smaller for gestational age and lower birth-weight relative to controls). In addition, premature delivery has also been associated with use.

There is evidence of an association with longer-term developmental neurobehavioural and neurocognitive deficits in children up to 14 years of age (learning disabilities, poor attention and memory impairment). Decreased volume of the associated subcortical structures has also been demonstrated in these children. Although, once again, confounding biological and social factors cloud interpretation, these substances are likely to be neurotoxic to the developing brain.

Neonatal withdrawal has also been frequently recorded but appears usually to be self-limiting.

Revised October 2008. ©Therapeutic Guidelines Limited (etg35demo, November 2011)