Is caffeine safe during pregnancy?

Caffeine is a widely consumed stimulant, which can be consumed in several forms (e.g. coffee, energy drinks, etc.), is one of the most commonly used psychoactive substance worldwide ¹⁾. Recent data from nationally representative samples indicate about 89% of American adults consume caffeinated products daily with virtually no difference between men and women in how frequently the products are used ²⁾. Caffeine is a naturally occurring alkaloid substance found in numerous plant species with coffee beans, tea leaves, cocoa beans, and kola nuts are the primary natural sources of this compound ³⁾. Caffeine is added to numerous foods and beverages (e.g., soft drinks and energy drinks). Chocolate and cocoa ⁴⁾ are also sources of caffeine, as are certain dietary supplements ⁵⁾ and medications ⁶⁾.

Maternal caffeine intake has repeatedly been linked to babies being born small for gestational age (SGA) ⁷⁾. Moderate prenatal caffeine exposure (< 200 mg/day) does not seem to impair neonatal health, although prenatal caffeine exposure is associated with the child being born small for gestational age (SGA) and small for gestational age (SGA) is strongly associated with impaired neonatal health ⁸⁾. However, no significant associations between maternal caffeine intake and neonatal health were found. Evidence from rodent studies demonstrated that in utero caffeine exposure triggered cardiometabolic defects on both the immediate offspring and subsequent generations. Further studies are needed regarding caffeine’s long-term effects and multigenerational influence in humans ⁹⁾. High levels of caffeine in pregnancy can result in babies having a low birthweight, which can increase the risk of health problems in later life. Too much caffeine can also cause a miscarriage. So, if you’re pregnant, limit the amount of caffeine you have to 200 milligrams (mg) a day. This is about the same as 2 mugs of instant coffee.

The amount of caffeine found in some foods and drinks is as follows:

• 1 mug of instant coffee: 100mg
• 1 mug of filter coffee: 140mg
• 1 mug of tea: 75mg
• 1 can of cola: 40mg
• 1 can (250ml) of energy drink: up to 80mg – larger cans may contain up to 160mg
• 1 bar (50g) of plain chocolate: most products on the UK market contain less than 25mg
• 1 bar (50g) of milk chocolate: most products on the UK market contain less than 10mg

In a day, you will almost reach your 200mg caffeine limit if you have:

• 2 mugs of tea and 1 can of cola
• 1 mug of instant coffee and 1 can (250ml) of energy drink

Reducing your caffeine intake

• Try water, fruit juice, or decaffeinated tea or coffee. Limit the amount of energy drinks you have, as they can be high in caffeine.
• If you occasionally exceed the recommended limit, don’t worry. The risks are quite small.
• Always talk to your doctor before taking any medicines in pregnancy, including cold and flu remedies.

What is the relationship between usual caffeine consumption and pregnancy outcomes?

There is a consistent evidence from observational studies indicating that caffeine intake in pregnant women is not associated with risk of preterm delivery. Higher caffeine intake (especially >=300 mg/day ) is associated with a small increased risk of miscarriage, stillbirth, low birth weight, and small for gestational age births. However, these data should be interpreted cautiously due to potential recall bias in the case-control studies and confounding by smoking and pregnancy signal symptoms.

Regular use of large amounts of caffeine have been associated with reduced fertility in both women and men ¹⁰⁾. A meta-analysis of studies involving approximately 50,000 pregnant women in total suggested a slightly elevated rate of spontaneous abortion amongst women who drank more than 150 mg of caffeine per day during pregnancy ¹¹⁾. Stefanidou ¹²⁾ reported a dose-response relationship between caffeine ingestion and recurrent miscarriage. After controlling for confounders, the odds ratio for recurrent miscarriage increased with increased daily caffeine intake in the periconceptional period and in early gestation. A prospective Danish study found a slight elevated rate of stillbirth amongst pregnant women who had consumed more than eight cups of coffee a day ¹³⁾. A follow-up study by the same authors demonstrated that women who drank more than eight cups of coffee per day were at increased risk of a fetal death ¹⁴⁾.

Key Findings

Consumption of caffeine from various sources was associated with a significantly increased risk of spontaneous abortion and low birth weight ¹⁵⁾. Control for confounders such as maternal age, smoking, and ethanol use was not possible.

Two studies assessed observational studies on the association of caffeine intake with adverse pregnancy outcomes ¹⁶⁾, ¹⁷⁾. The pregnancy outcomes included miscarriage, pre-term birth, stillbirth, small for gestational age and low birth-weight. The most recent study by Greenwood et al. ¹⁸⁾ quantified the association between caffeine intake and adverse pregnancy outcomes from 60 publications from 53 separate cohort and case-control studies. The evidence covered a variety of countries with caffeine intake categories that ranged from non-consumers to those consuming >1,000mg/day. They found that an increment of 100 mg caffeine was associated with a 14% increased risk of miscarriage, 19% increased risk of stillbirth, 10% increased risk of SGA, and 7% increased risk of low birth weight. There was no significant increase in risk of preterm delivery. The magnitude of these associations was relatively small within the range of caffeine intakes of the majority women in the study populations, and the associations became more pronounced at higher range (>=300 mg/day). The authors also note the substantial heterogeneity observed in the meta-analyses shows that interpretation of the results should be cautious. In addition, the results from prospective cohort studies and case-control studies were mixed together. Since coffee consumption is positively correlated with smoking, residual confounding by smoking may have biased the results toward a positive direction ¹⁹⁾.

The other studies did not cover all of the above pregnancy outcomes, but for those adverse outcomes covered, the results were in agreement with Greenwood et al., Maslova ²⁰⁾ reviewed 22 studies (15 cohort and 7 case-control studies) and found no significant association between caffeine intake and risk of pre-term birth in either case-control or cohort studies. For all of the observational studies assessed across the three studies, most studies did not adequately adjust for the pregnancy signal phenomenon, i.e. that nausea, vomiting, and other adverse symptoms are associated with a healthy pregnancy that results in a live birth, whereas pregnancy signal symptoms occur less frequently when the result is miscarriage. Coffee consumption decreases with increasing pregnancy signal symptoms, typically during the early weeks of pregnancy, and this confounds the association. Greenwood et al. ²¹⁾ state that this potential bias is the most prominent argument against a causal role for caffeine in adverse pregnancy outcomes. Only one randomized controlled trial of caffeine/coffee reduction during pregnancy has been conducted to date. The study found that a reduction of 200 mg of caffeine intake per day did not significantly influence birth weight or length of gestation. The trial did not examine other outcomes.

A number of studies have demonstrated an increased rate of cryptorchidism, anal atresia and cleft lip/palate amongst infants whose mothers consumed caffeine during pregnancy; however, these studies were limited by retrospective exposure assessment, small sample size and failure to adjust for other potential confounders including maternal smoking and alcohol consumption ²²⁾. A study by Schmidt ²³⁾ identified an association between infant neural tube defect (NTD) risk and polymorphisms in a fetal and maternal gene involved in caffeine metabolism. The authors suggested that risk of neural tube defects may be increased in genetically susceptible individuals with caffeine consumption.

The data relating to the effects of caffeine on fetal growth in utero are mixed. Numerous studies ²⁴⁾, ²⁵⁾, ²⁶⁾ have suggested a link between intrauterine growth restriction (IUGR) or low infant birth weight and caffeine consumption in pregnancy. A meta-analysis from 1998, which included approximately 50,000 pregnant women, suggested a slightly increased risk of having a baby with intrauterine growth restriction (IUGR), if the mother had consumed more than 150 mg of caffeine per day ²⁷⁾. More recent studies have also found a positive correlation between caffeine intake and low birth weight ²⁸⁾ found reduced infant birth weight with maternal daily caffeine intake of more than 540 mg, whilst Sengpiel ²⁹⁾ reported that maternal caffeine intake of more than 200 mg to 300 mg/day increased the odds for having a small for gestational age infant. Other studies have suggested that effects of maternal caffeine consumption on birth weight are restricted to male offspring only ³⁰⁾, or to infants of women who are rapid caffeine metabolizers ³¹⁾. However, a review of the literature in 2000 demonstrated no evidence of an effect of even moderate to high caffeine consumption on in utero growth ³²⁾ and another concluded that low infant birth weight cannot be clearly attributed to caffeine and cannot be separated from effects of other exposures such as maternal smoking and alcohol consumption ³³⁾.

Regular coffee consumption during pregnancy has recently been associated with childhood acute leukemia in the offspring in a single study, with the risk increasing linearly with daily intake ³⁴⁾.

A New Zealand study ³⁵⁾ reported that the babies of women who consumed greater than 400 mg of caffeine per day during pregnancy were 1.65 times more likely to die of sudden infant death syndrome than the babies of women who consumed less caffeine. The New Zealand study ³⁶⁾ also found that infants born to women who consumed high quantities of caffeine whilst pregnant were more likely to experience sleep apnea (difficulty breathing during sleep).

Summary

There is insufficient robust scientific evidence on which to provide a specific recommendation regarding the amount of caffeine that can be consumed during pregnancy without causing harm to the fetus. The data regarding caffeine consumption during pregnancy are contradictory. An association between caffeine intake and increased miscarriage risk, and possibly fetal demise has been reported but remains unproven. Similarly, various structural anomalies have been reported following caffeine exposure in utero but a causal association or consistent embryopathy has not been demonstrated.

Maternal caffeine consumption of less than 150 mg caffeine a day in pregnancy does not appear to affect fetal growth, and although an adverse effect on birth weight has been reported at higher doses by some, these data are inconsistent with respect to identifying a threshold dose for this effect. Single studies have suggested a possible association with childhood acute leukemia and hyperactivity, but these findings remain to be confirmed.

Pregnant women who consume more than 200 mg of caffeine daily (about two cups of brewed coffee) should reduce their caffeine consumption whilst pregnant. Health professionals advise individuals to reduce their caffeine consumption gradually, for example by replacing one caffeinated drink with a non-caffeinated alternative each day, in order to avoid withdrawal symptoms. Decaffeinated varieties are an option which contains little or no caffeine.

Energy drinks are not recommended during pregnancy as they may contain high levels of caffeine, and other ingredients not recommended for pregnant women.

What is Caffeine ?

Caffeine (1,3,7-trimethylxanthine) is an adenosine and benzodiazepine receptor antagonist, phosphodiesterase inhibitor, and central nervous system stimulant ³⁷⁾, ³⁸⁾. Caffeine is a pharmacologically active component of many foods, beverages, dietary supplements, and drugs; it is also used to treat very ill newborns afflicted with apnea (temporary cessation of breathing) ³⁹⁾. Caffeine occurs naturally in some plant leaves, seeds, and fruits, where it serves as an herbicide, insect repellant, and even attractant for pollination ⁴⁰⁾. This botanically sourced compound is the most commonly consumed stimulant worldwide ⁴¹⁾. Caffeine enters the human food chain through plant-derived foods such as coffee beans, tea leaves, guarana, cocoa beans, and kola nuts ⁴²⁾. In healthy adults, a caffeine intake of ≤400 mg/day is considered safe; acute clinical toxicity begins at 1 g, and 5 to 10 g can be lethal ⁴³⁾.

Caffeine is the world’s most popular drug, and coffee is possibly the second most valuable product after oil. The common dietary sources of caffeine are coffee, chocolate, tea, and some soft drinks. The amount of caffeine in food products varies, depending on the serving size, the type of product and the preparation method ⁴⁴⁾. Up to 90% of Americans of all ages consume some caffeine daily with more than 50% consuming coffee daily ⁴⁵⁾. More than 50% average 300mg caffeine per day, with an average daily dosage for all consumers of about 200mg. One report estimates nearly 95% of Brazil’s population consumes caffeine daily, whereas only about 63% of Canadian adults do so. The average dietary caffeine consumption in some Scandinavian countries is more than 400 mg per person per day. It is not hard to reach 200-300mg of caffeine daily since a standard eight-ounce cup of coffee made by the American drip method contains between 125mg and 250mg of caffeine. A 12-ounce can of Coca-Cola contains 34mg. Also, the usual ‘cup’ of coffee for many individuals is often actually 12 or even 16 ounces and sometimes more.

Most people consume caffeine from drinks. The amounts of caffeine in different drinks can vary a lot, but it is generally:

• An 8-ounce cup of coffee: 95-200 mg
• A 12-ounce can of cola: 35-45 mg
• An 8-ounce energy drink: 70-100 mg
• An 8-ounce cup of tea: 14-60 mg

Caffeine has many effects on your body’s metabolism

• Caffeine stimulates your central nervous system, which can make you feel more awake and give you a boost of energy.
• Caffeine is a diuretic, meaning that it helps your body get rid of extra salt and water by urinating more.
• Caffeine increases the release of acid in your stomach, sometimes leading to an upset stomach or heartburn.
• Caffeine may interfere with the absorption of calcium in the body.
• Caffeine increases your blood pressure.

Within one hour of eating or drinking caffeine, it reaches its peak level in your blood. You may continue to feel the effects of caffeine for four to six hours.

For most people, it is not harmful to consume up to 400mg of caffeine a day. If you do eat or drink too much caffeine, it can cause health problems, such as:

• Restlessness and shakiness
• Insomnia. Most adults need seven to eight hours of sleep each night. But caffeine, even in the afternoon, can interfere with this much-needed sleep. Chronically losing sleep — whether it’s from work, travel, stress or too much caffeine — results in sleep deprivation. Sleep loss is cumulative, and even small nightly decreases can add up and disturb your daytime alertness and performance. Using caffeine to mask sleep deprivation can create an unwelcome cycle. For example, you may drink caffeinated beverages because you have trouble staying awake during the day. But the caffeine keeps you from falling asleep at night, shortening the length of time you sleep.
• Headaches
• Dizziness
• Rapid or abnormal heart rhythm
• Stomach upset
• Dehydration
• Anxiety
• Dependency, so you need to take more of it to get the same results.

Some people are more sensitive to the effects of caffeine than others. If you’re susceptible to the effects of caffeine, just small amounts — even one cup of coffee or tea — may prompt unwanted effects, such as restlessness and sleep problems. How you react to caffeine may be determined in part by how much caffeine you’re used to drinking. People who don’t regularly drink caffeine tend to be more sensitive to its negative effects. Other factors may include genetics, body mass, age, medication use and health conditions, such as anxiety disorders.

Do not underestimate the power or potency of caffeine. An abrupt decrease in caffeine may cause withdrawal symptoms, such as headaches, fatigue, irritability and difficulty focusing on tasks. Fortunately, these symptoms are usually mild and resolve after a few days. Caffeine dependency can occur after as little as seven days of exposure. 100mg per day can sustain dependency. In fact, many individuals can avoid caffeine withdrawal symptoms by as little as 25mg—the equivalent of about two tablespoons of most “gourmet” coffees. Carefully controlled studies show that caffeine doses as low as about 10mg can be reliably noticed by particularly sensitive people. These studies also show that more than 30 percent of people can feel the effects of 18mg or less.

Studies of caffeine dependency and tolerance show that daily caffeine users are actually more motivated to consume it to avoid withdrawal symptoms, than to experience the lift that its stimulant properties may provide. Caffeine’s combination of a punishing syndrome of withdrawal, along with a rewarding sense of wakefulness, has made coffee, tea, and chocolate, some of humanity’s best-loved foods. One might say that caffeine-producing plants have succeeded in motivating humans to cultivate them widely and with very great care.

Not everyone consuming daily caffeine is equally likely to develop dependency and withdrawal syndrome. Studies indicate that genetics make some people more likely than others. Scientists do not know whether the inherited tendency to experience caffeine withdrawal syndrome relates to the genetic factors that cause migraine. In summary, caffeine may lead to the development of medication-overuse headache (so-called “rebound” headache). As such, patients should limit caffeine use as recommended for other acute medications for migraine. This use should not exceed two days per week. Removing caffeine alone is rarely enough to solve the problem. For patients with high daily caffeine intake, this reduction in use should be achieved over a gradual taper of days or even weeks to limit the impact of withdrawal syndrome.