Women who are pregnant should better stay clear of coffee and other caffeinated drinks. According to a systematic review of 1,261 peer-reviewed articles linking caffeine to pregnancy outcomes, there is no safe level of consumption.

Caffeine (1,3,7-trimethylxanthine), the main stimulant found in coffee — but also in tea, soft drinks, chocolate, and some nuts — has many metabolic effects. Besides caffeine, coffee contains other substances with important metabolic effects such as theobromine (main stimulant found in cocoas), theophylline (may be good for treating asthma), and chlorogenic acid (may slow down carbohydrate absorption).

What’s quite possibly the most popular psychoactive substance in history, caffeine seems to provide more benefits and downsides. Studies suggest that three to four cups of coffee per day reduced the risk of type 2 diabetes, metabolic syndrome, kidney stones, gout, and several types of cancer, including endometrial, skin, prostate, and liver cancer.

However, this doesn’t mean that caffeine is advisable for all people. In a new study, Professor Jack James of Reykjavik University in Iceland, along with colleagues, combed through 1,261 articles in the English-speaking scientific literature relating to caffeine and pregnancy outcomes.

This huge roster of studies was whittled down to 48 original observational studies and meta-analysis published in the past two decades. The studies reported on one or more of six major negative pregnancy outcomes: miscarriage, stillbirth, low birth weight and/or small for gestational age, preterm birth, childhood acute leukemia, and childhood overweight and obesity.

According to the analysis, 32 observational studies found that caffeine is significantly associated with adverse pregnancy outcomes, while 10 studies found no or inconclusive associations.

Eleven studies included in the review reported on the findings of 17 meta-analyses (studies of other studies), 14 of which concluded maternal caffeine consumption was associated with increased risk of miscarriage, stillbirth, low birth weight, and small gestational age, and childhood acute leukemia.

Although no meta-analyses found an association between maternal caffeine consumption and childhood obesity, four observational studies reported a significant association.

In conclusion, the authors of the review write that there is “substantial cumulative evidence” pointing towards a link between maternal caffeine consumption and adverse negative pregnancy outcomes.

This runs counter to official guidelines for caffeine consumption for pregnant women in the United States and other countries. The UK NHS, the American College of Obstetricians and Gynecologists, the Dietary Guidelines for Americans, and the European Food Safety Authority (EFSA) all claim that moderate caffeine intake shouldn’t do harm to babies. These health organizations advise consuming no more than 200 mg caffeine, which is equivalent to two cups of moderate-strength coffee per day.

In contrast, the authors of the new study advise avoiding caffeine altogether for pregnant women or even those looking to conceive. As a result, the researchers call for a “radical revision” of current health recommendations, even though their assessment is purely observational and does not speak of any cause-effect.

“Specifically, the cumulative scientific evidence supports pregnant women and women contemplating pregnancy being advised to avoid caffeine,” James said in a statement.

The findings appeared in the journal BMJ Evidence Based Medicine.