The UK Food Standards Agency (FSA) has issued a press release advising pregnant mothers to limit their intake of coffee and caffeine-containing substances.[1] "Pregnant women are advised to limit their daily caffeine intake to 200mg a day – roughly two mugs of coffee a day" due to a potential link with Foetal Growth Retardation (FGR). This is a reduction from the previous advice of 300 mg per day, following an updated report from the FSA's independent Committee on Toxicity (COT).[2] According to the committee, if there is a causal link then there may be no lower 'safe' limit, but a caffeine intake of less than 200 mg per day during pregnancy may reduce the risk of FGR to less than 2%. FGR is defined as failure of the baby to attain its growth potential as determined by genetic and environmental factors.

The FSA funded research published by the British Medical Journal[3] which measured caffeine intake from all sources (coffee, tea, colas and medication) in pregnant women, and then measured their babies when they were born. The xenobiotic caffeine can be detoxified from the body in four main ways, 3-demethylation being quantitatively the most important: caffeine is converted to paraxanthine by the enzyme cytochrome P450 1A2 (CYP1A2). This is one of the enzymes which often has low activity in the GT4 Explorer GenoType, and is responsible for Explorers being up all night after drinking coffee. The researchers measured the CYP1A2 enzyme activity as the main form of caffeine clearance in the mothers taking part in the study. They found that the mothers with the highest CYP1A2 activity passed the most caffeine and caffeine metabolites to their foetus via the placenta. CYP1A2 activity is absent in the placenta and the fetus.[4] This means that like the GT4 Explorer, the unborn baby won't get much sleep after their mother has drunk coffee.

What is the problem with having smaller babies? It is a well known epigenetic risk factor, as the COT study says:

FGR is an important outcome because it is associated with an increased risk of perinatal mortality and morbidity, including perinatal asphyxia. Moreover, there is epidemiological evidence that FGR correlates with adverse effects in adult life. For example, affected individuals have an increased incidence of metabolic syndrome, manifesting as obesity, hypertension, hypercholesterolemia, cardiovascular disease, and type 2 diabetes.

Smoking and alcohol intake also have a significant effect on the risk of FGR.

References:

1. Food Standards Agency. "Food Standards Agency publishes new caffeine advice for pregnant women." Press release, Monday 3 November 2008.
2. Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. "Statement on the reproductive effects of caffeine". COT statement 2008/04
3. CARE Study Group. "Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study" BMJ 2008;337:a2332
4. Aldridge A, Aranda JV, Neims AH. "Caffeine metabolism in the newborn." Clin Pharmacol Ther. 1979 Apr;25(4):447-53. PMID: 428190