Coffee controversy brews on.

What did they do?

Wendler and colleagues investigated if caffeine exposure during early embryo development affects how the heart forms and how it functions later in life.

Pregnant mice were treated with caffeine and either normal air conditions or under low oxygen levels to create a hypoxic environment. Low oxygen levels are known to impact cardiovascular development. 

Pregnant mice were put into one of four treatment groups: normal oxygen, normal oxygen + caffeine, low oxygen, and low oxygen + caffeine.

The treated mice received a single injection of 20 milligrams per kilogram caffeine. This dose was selected because it leads to blood concentrations of caffeine that are about equal to levels found in humans after two cups of coffee.

Embryos from the treated mice were compared to embryos from untreated mice to determine the effects of caffeine and hypoxia on heart development and function, body growth and body fat. Two key proteins important in maintaining oxygen balance were also evaluated to assess differences in genomic responses among the groups.

What did they find?

Exposure to a single dose of caffeine during embryo development results in both short-term effects on cardiac development and long-term effects on cardiac function.

In this study, the prenatal caffeine exposure influenced cardiac development and heart performance later in life, altered protein function and changed body fat composition in male mice. Alone, the caffeine inhibited heart muscle development by 37 percent in the embryos. It also reduced expression by 40 percent of a key protein -- the oxygen balancing protein, HIF1α -- that plays an important role in managing responses when oxygen supplies are low. 

Stronger effects were seen when embryos were exposed to both caffeine and low oxygen conditions.

When tested together, caffeine and hypoxia disrupted proper heart development by 53 percent and was observed as thinner heart walls. In the exposed offspring reared to adults, heart function -- as measured by echocardiography -- was impaired by 38 percent due to a reduced ability to contract. The cause for the reduction has yet to be determined.

Male mice from both groups exposed to caffeine -- with either normal or low oxygen conditions -- had 20 percent more fat when compared to their respective controls.

As expected, hypoxia alone retarded embryonic body growth by 30 percent but did not cause embryo malformations. Birth weights among the groups were similar, though, so the growth effects were short lived, disappearing after normal oxygen levels were restored.

What does it mean?

A one-time exposure to caffeine while in the womb can have adverse short and long-term health consequences for a developing mouse. Heart development and function were impaired in embryos exposed through their mothers to a single dose of caffeine at levels that are commonly perceived to be safe. The effects intensified under low oxygen conditions.

These findings add more information to the debate about whether caffeine affects heart health. The results of this animal study suggest that caffeine exposure before birth can affect heart function later in life. These observations in mice may not be directly relevant to human health or disease.

Caffeine and its metabolites can easily cross the placenta but womb levels are usually lower than the mothers. Embryos are less able to process caffeine than adults, which means exposure times may increase and the consequences may be greater.

Maternal caffeine concentrations peak between between 30 and 60 minutes then quickly plummet as the caffeine metabolized, usually within 6 hours. During pregnancy, it can take as long as 20 hours to process, exposing the developing embryo and fetus to its effects for up to 10 times as long (200 hours).

Many women could consume caffeine through coffee, sports drinks or other soda drinks in early pregnancy before they know they are pregnant. Recent studies show there is an increased miscarriage rate associated with early pregnancy exposure to caffeine.

It also has direct effects on maternal heart function, blood flow and/or placental transfer. The impact on the mother's system could underlie the adverse effects observed in the mouse embryos prenatally exposed to caffeine.

But, other studies report caffeine can be beneficial and find it plays a role in cancer prevention and improves neurological or immunological disorders.

Because of conflicitng findings, more research is needed to better understand the impacts of caffeine on human health, especially during pregnancy and on development.