Most current studies have shown that caffeine consumption less than 200 to 300 milligrams (mg)/day is not associated with negative outcomes of pregnancy, to include birth defects, miscarriage, or preterm birth.
This does not mean that amounts over 300 mg/day will cause problems, but that aiming for under this amount minimizes risk as much as possible, as outcomes associated with 400 mg/day and higher are less certain. The minimum amount of caffeine per day in which negative outcomes may start to appear is not known.
This has recently been debated again, as at least three recent studies (2020-2021) have concluded that even amounts below 200 mg/day may have some adverse effects, particularly on fetal growth (these studies are detailed below).
However, overall, research regarding the effects of caffeine on pregnancy outcomes remains very inconsistent. This inconsistency is due to the difficulty – if not impossibility – in not only defining caffeine intake consistently across all studies, but determining accurate caffeine consumption across a pregnancy while controlling for all potential confounders and biases (other dietary/environmental aspects that could have caused or contributed to the identified adverse effects).
Caffeine is a very popular and frequently consumed drug in the general population; the sheer volume of publications, together with the research hurdles described below, makes it very difficult to determine the safety of caffeine during pregnancy.
While some research indicates women should avoid caffeine altogether, various obstetric organizations stand by their prior recommendations that less than 200 mg/day is likely not a concern. Women should talk to their health care provider (HCP) if they have any questions or concerns.
Background
Caffeine is the most consumed active stimulant in the world; it is estimated about 80% of pregnant women consume caffeine daily in various food and beverages. There is a lot of research on this topic based on this high consumption; however, it is also a cause of confusion for HCPs and the general public due to a significant amount of conflicting research, mixed messaging, and selective dramatic headlines.
Caffeine: Caffeine is a plant compound and central nervous system stimulant present in different types of beverages and food items such as coffee, tea, soft drinks and chocolate, as well as certain medications.
Effects: Caffeine’s primary mechanism of action is on the adenosine receptors in the brain; however, there are adenosine receptors throughout the body. As such, caffeine consumption is associated with a wide spectrum of (mild to moderate) symptoms, including anxiety, restlessness, fidgeting, irritability, headache, nausea, vomiting, fever, tremors, hyperventilation, dizziness, and a ringing in the ears.
Tolerance: occurs with repeated dosing over several days; individuals not used to caffeine can have more complications than those who are used to consuming it.
Withdrawal: opposite of tolerance; reported as sleepiness and fatigue; can occur as quickly as 24 hours when an individual's "normal" daily amount of caffeine is not consumed.
Mechanism
It takes pregnant women a longer period to clear caffeine from their systems, and it takes fetuses and preterm infants even longer. Although metabolisms vary, the half-life of caffeine is approximately five hours in the average adult.
Pregnant women, especially those in the final trimester, may have a prolonged half-life upwards of 10 to 15 hours while fetuses and preterm infants may experience a half-life of 50 to 100 hours. Full term newborns have a caffeine half-life approximately 8 to 30 hours.
The primary enzyme that metabolizes caffeine (Cyp1A2) is not present in the human placenta, fetus, or the newborn. Further, maternal Cyp1A2 activity slows down in the second and third trimesters which is why half-life is increased in pregnancy.
Caffeine passes through the placenta freely where the fetus is unable to metabolize it (the liver is one of the last fetal organs to develop); daily maternal caffeine consumption could therefore cause it to build up in the fetus. Caffeine can also enter the amniotic fluid and umbilical cord.
There have also been several cases of caffeine withdrawal reported in infants whose mothers consumed very high amounts of caffeine (greater than 800 mg/day).
Research Hurdles
Based on caffeine’s effects on humans and its ability to pass to the fetus, many studies have been conducted to determine possible adverse effects on reproductive outcomes.
However, despite thousands of published papers illustrating both positive and negative effects of caffeine on the general population, caffeine's' effects on pregnancy remain very difficult to assess:
The sheer volume of publications has led to enormous inconsistency, mostly due to the resulting outcome of each individual study.
For example, some studies assess birth defects in general, while others focus on only one specific defect; others may focus on specific fetal effects, while others may assess the risk of maternal complications, such as preterm delivery or preeclampsia. (Note: These hurdles are not specific to caffeine. Learn more.)
Further, research conclusions cover a wide range of possible outcomes: some authors have concluded caffeine intake is harmful, even causing stillbirth and fetal death, while others indicate it has no effect on these outcomes; others claim that caffeine may actually be beneficial in reducing the risk of complications such as gestational diabetes or preeclampsia, while others say caffeine has no benefit on these outcomes.
It is also possible that similarly to alcohol, possible adverse effects that occur with less than 200 to 300 mg/day of caffeine may be too subtle for science to recognize as being the result of caffeine consumption during pregnancy.
Researchers also have to account for numerous potential biases; eliminating this long list of biases can be impossible.
Many caffeine-related studies rely on self-administered questionnaires, sometimes months, even years after delivery.
Further, compared to the mothers of healthy newborns, mothers of children with a congenital malformation may be more inclined to remember and exaggerate caffeine consumption, while mothers with healthy newborns may underreport their caffeine consumption.
Additionally, inconsistent prenatal caffeine studies that included findings such as childhood cancers were identified to have problems with design related to improper control for recall bias.
There is also no consistent definition regarding a cup of coffee. How many ounces and how much caffeine constitutes a cup? What about the strength or type of brew? Were milk, cream, sugar, or artificial sweeteners added? Was it consumed with food or by itself first thing in the morning? Is the woman used to caffeine? What was her caffeine consumption prior to pregnancy?
Additionally, other factors may also be at play, to include the mother’s metabolism or if the mother also smoked or drank alcohol. Some studies even suggest the identified negative outcomes related to caffeine could be from other chemicals in coffee or tea, and not necessarily the caffeine.
Lastly, regarding caffeine and an association with miscarriage, there is a phenomenon to consider known as the “pregnancy signal”.
Women suffering from nausea and vomiting of pregnancy and aversions to tastes and smells are already considered to have less risk of miscarriage than those not suffering from these early symptoms. These women are also less likely to consume caffeine, especially through coffee. If this is not accounted for, it can skew results.
Pregnancy/Fetal Effects
Current data does not appear to demonstrate consistent adverse effects following consumption of caffeine at intakes up to 300 mg/day in healthy pregnant women. However, many organizations set their recommended daily limit at 200 mg/day.
Miscarriage: Again, although inconsistent and dealing with the same research hurdles as described above, many studies have not found an association between miscarriage and caffeine at levels below 300 mg/day; those that did found an association at much higher levels.
For example, a study published in February 2018 that included 15,590 pregnancies found that women consuming greater than or equal to four [coffee] servings/day had a 20% increased risk of miscarriage (particularly at weeks 8-19).
Further, in general, it as assessed that while miscarriages are very common, the vast majority are caused by chromosomal abnormalities, with a much smaller amount due to outside factors, such as foods, drugs, or chemicals.
Theories for why caffeine could be associated with adverse outcomes is based on whether caffeine affects uterine and placental blood flow, resulting in less oxygen to the fetus. However, even this remains debated, and most studies that found an association between caffeine and uterine/placental blood flow found it, again, with levels higher than 300 mg/day.
Fetal growth: The mechanism for how caffeine could affect fetal growth is the same as miscarriage: constriction of blood vessels in the uterus and/or placenta.
A review of existing studies and meta-analyses of maternal caffeine consumption from the past twenty years published in August 2020 concluded that maternal caffeine consumption is "reliably associated with major negative pregnancy outcomes" and with "no threshold of consumption below which associations were absent" (no minimum safe amount). The author concluded that pregnant women and those trying to conceive should avoid caffeine.
However, the author also noted that the reported findings were "robust to threats from potential confounding and misclassification" (as described above under Research Hurdles).
Other researchers indicated the study was "too alarmist" due to the significant limitations of the review and, in general, of studying caffeine. Further, most of the women in the original studies that were reviewed were asked about their caffeine consumption long after delivery.
A study published in March 2021 of 2,055 women from 12 clinical sites found that increased caffeine consumption was significantly associated with lower birth weight, shorter length, and smaller head, arm, and thigh circumference in the newborn – even at amounts less than 200 mg/day.
This study determined that even small increases in plasma caffeine concentrations and its major metabolite paraxanthine, negatively affected fetal growth.
Therefore, small-for-gestational (SGA) age may have the most consistent findings. This is assessed to possibly be a "less severe" type of SGA that is not consistently associated with long-term complications, but more research is needed. Further, it is not clear if these associations can be found across trimesters. (For example, is fetal growth affected more due to caffeine consumption in the first trimester vs. the third trimester?)
Neurodevelopment: A study published in January 2021 (using MRI data of 9,157 children, aged 9-10 years) determined that gestational caffeine exposure can lead to future neurodevelopmental complications and that this occurs, in part, through alteration of the microstructure of critical fiber tracts in the brain. According to the study authors, "these data suggest that current guidelines regarding limiting caffeine intake during pregnancy may require some recalibration."
A study published in July 2021 evaluated 9,978 children between 9 and 11 years old with known prenatal caffeine exposure and determined that this exposure (in a dose dependent manner) was associated with brain structural changes that could adversely effect their cognitive functioning. However, tying prenatal caffeine exposure and functional development 9 to 11 years after delivery is difficult, and more research is necessary.
Despite the above recent research, obstetric organizations have not changed their recommendations that women try to limit their daily caffeine consumption to less than 200 mg/day, largely due to major inconsistencies across studies.
In general, researchers have advocated a need to conduct high-quality, double-blinded random clinical trials to determine whether caffeine has any effect on pregnancy outcome.
Action
Many health organizations make the same recommendation: pregnant women should limit caffeine to 200 mg/day to minimize potential risks as much as possible, especially due to the vast inconsistency of current published studies and reviews. Women should talk to their HCP if they have any questions regarding caffeine and pregnancy.
Resources
Moderate Caffeine Consumption During Pregnancy: Committee Opinion 462 (American College of Obstetricians and Gynecologists; 2016)
Restricting caffeine intake during pregnancy (World Health Organizations)
Caffeine Fact Sheet (MotherToBaby.org; 2019)
Exploring Maternal Patterns of Dietary Caffeine Consumption Before Conception and During Pregnancy (Matern Child Health J; 2014) Immediate download
Caffeine Chart (Center for Science in the Public Interest)