Scenario: 27 yo G1P0 presents to your office for her prenatal appointment. She is currently 8 weeks pregnant and this is her first prenatal visit. She mentions she’s been doing a lot of research online about what her diet should be like. She says she’s read that she should limit her caffeine intake to one cup of coffee a day, but is wondering if completely eliminating caffeine further decreases any potential risks to her baby?
Clinical Question: Does prenatal maternal caffeine intake increase the risk of childhood obesity?
What type of scenario is this?
□ Therapy/ Intervention □ Diagnosis □ Etiology □ Prognosis □ Screening □ Prevalence
□ Harms
Assuming that the highest level of evidence to answer your question will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)? Please explain your choices.
I will likely be looking for observational studies that follow women throughout pregnancy, monitoring their caffeine intake and observing the outcomes. The mothers and offspring will have to be followed over a longer period of time, making a cohort study a likely finding. I will be looking for cohort studies, either prospective or retrospective, that monitor caffeine intake and assess the obesity-related outcomes of the children over time. While a randomized controlled trial might show the best evidence for the risks of caffeine consumption by measuring caffeine doses and comparing to a placebo, I imagine it is unlikely I will find any as it seems unethical to potentially put a fetus at risk intentionally, and then difficult to follow over such a long period.
Search Strategy:
PICO Search Terms
| P | I | C | O |
| Pregnant women | Maternal caffeine consumption | No caffeine intake | Risk of childhood obesity |
| Prenatal period | Caffeine intake | No intake | Overweight childhood |
| Pregnancy | Maternal caffeine intake | Increased children BMI | |
| Maternal | Prenatal caffeine consumption | Childhood adiposity |
Filters Applied:
- Recent publications within the past 5 years
- Recent publications within the past 10 years
- Review
- Full Article
- Journal
Databases Used:
- PubMed
- ScienceDirect
- Wiley Online Library
- Google Scholar
Results:
| Database | Filter | Articles Returned | |
| PubMed | English/Last 5 years/Full Text/Full Article/ | maternal caffeine intake and risk of childhood obesity | 456 |
| ScienceDirect | English/ 2010-2021/ Research Articles | maternal caffeine intake and childhood obesity risk | 304 |
| Wiley Online Library | English/ 2015-2021/ Journals | maternal caffeine intake and risk of childhood adiposity | 204 |
| Google Scholar | 2010-2020/Include patents/Include Citations | prenatal exposure to caffeine and risk of childhood obesity | 17,700 |
I narrowed down these results by choosing the most up to date studies I could find, with the oldest study chosen being published in 2017. I chose studies that were either systematic reviews or population-based cohort studies. I felt these were the best studies as they followed patients over time and were able to show the impacts on children from maternal caffeine intake during pregnancy. I chose studies that looked directly at childhood obesity as the outcome, and were directly related to maternal caffeine intake. I wanted studies that were recent with large sample sizes that could allow for application of results across various populations and demographics.
Articles Chosen for Inclusion:
| Article #1 | |
| Citation | Frayer NC, Kim Y. Caffeine Intake During Pregnancy and Risk of Childhood Obesity: A Systematic Review. Int J MCH AIDS. 2020;9(3):364-380. doi:10.21106/ijma.387 |
| Abstract | Objective: This paper evaluates the association between caffeine consumption during pregnancy and overweight or obesity in the offspring. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search was conducted using MedLine, PubMed, CINAHL-Plus and Google Scholar databases. Inclusion criteria were cohort studies on participants with live singleton births at ≥28 weeks gestation who had consumed caffeine during pregnancy. Included were studies reporting both measurement of maternal caffeine intake and offspring anthropometric measurements. Studies reporting serum paraxanthine, a measurement of caffeine intake, were also included. Results: After final elimination, there were eight studies meeting our inclusion criteria. From these studies, we deduced that caffeine intake during pregnancy between 50 mg and <150 mg/day was associated with increased risk of overweight and obesity by excess fat deposition or increased weight, and elevated BMI per International Obesity Task Force (IOTF) criteria using a reference population. The majority of studies reported the strongest association with maternal caffeine intake during pregnancy and overweight and obesity risk beginning at ≥300 mg/day. Conclusion: The risk of childhood overweight or obesity was associated with caffeine consumption at 50 mg/day during pregnancy with a stronger association at intakes ≥300 mg/day and higher. The current recommendation of <200 mg/day of caffeine during pregnancy is likely associated with lower risk of overweight or obesity in offspring but avoidance of the substance is recommended. |
| PDF Link | |
| Reason for Inclusion | I selected this article because it is a systematic review of prospective cohort populations in multiple countries that evaluated the association between caffeine consumption during pregnancy and the risk of obesity or overweight outcomes in offspring. It directly applied to my PICO question, and included 8 studies that evaluated caffeine intake during pregnancy. It included only singleton births and the primary outcome was the association of maternal caffeine intake during pregnancy and childhood obesity status. Secondary outcomes included overweight status in childhood, altered fat deposition, or altered childhood anthropometrics. The majority of children were followed until the age of 6-10 years. |
| Article #2 | |
| Citation | Papadopoulou E, Botton J, Brantsæter AL, et al. Maternal caffeine intake during pregnancy and childhood growth and overweight: results from a large Norwegian prospective observational cohort study. BMJ Open. 2018;8(3):e018895. Published 2018 Apr 23. doi:10.1136/bmjopen-2017-018895 |
| Abstract | Background: To study the association between maternal caffeine intake during pregnancy and the child’s weight gain and overweight risk up to 8 years. Methods: Participants: A total of 50 943 mothers recruited from 2002 to 2008 and their children, after singleton pregnancies, with information about average caffeine intake assessed at mid-pregnancy. Measure: Child’s body size information at 11 age points from 6 weeks to 8 years. We defined excess growth in infancy as a WHO weight gain z-score of >0.67 from birth to age 1 year, and overweight according to the International Obesity Task Force. We used a growth model to assess individual growth trajectories. Results: Compared with pregnant women with low caffeine intake (<50 mg/day, 46%), women with average (50–199 mg/day, 44%), high (≥200–299 mg/day, 7%) and very high (≥300 mg/day, 3%) caffeine intakes had an increased risk of their child experiencing excess growth in infancy, after adjustment for confounders (OR=1.15, 95% CI 1.09 to 1.22, OR=1.30, 95% CI 1.16 to 1.45, OR=1.66, 95% CI 1.42 to 1.93, respectively). In utero exposure to any caffeine was associated with higher risk of overweight at age 3 years and 5 years, while the association persisted at 8 years, only for very high exposures. Any caffeine intake was associated with increased body mass index from infancy to childhood. Children prenatally exposed to caffeine intake >200 mg/day had consistently higher weight. Very high caffeine exposures were associated with higher weight gain velocity from infancy to age 8 years. Conclusion: Any caffeine consumption during pregnancy is associated with a higher risk of excess infant growth and of childhood overweight, mainly at preschool ages. Maternal caffeine intake may modify the overall weight growth trajectory of the child from birth to 8 years. This study adds supporting evidence for the current advice to reduce caffeine intake during pregnancy. |
| PDF Link | |
| Reason for Inclusion | I selected this article because it was a recent article that evaluated the results from a prospective observational cohort study. While it was Norwegian based, it included 50,943 mothers which I felt was worth including because of such a large sample size available to evaluate. It looked at singleton pregnancies and evaluated caffeine intake at mid-pregnancy, following children after delivery at 6 months, 18 months, 36 months, 5 years, 7 years, and 8 years. The primary outcomes included excess infant weight gain, childhood overweight/obesity status, and childhood BMI. |
| Article #3 | |
| Citation | Voerman E, Jaddoe VW, Gishti O, Hofman A, Franco OH, Gaillard R. Maternal caffeine intake during pregnancy, early growth, and body fat distribution at school age. Obesity (Silver Spring). 2016;24(5):1170-1177. doi:10.1002/oby.21466 |
| Abstract | Objective: We examined the associations of maternal caffeine intake during pregnancy with offspring growth patterns, and body fat and insulin levels at school-age. Methods: In a population-based birth cohort among 7,857 mothers and their children, we assessed maternal caffeine intake during pregnancy by questionnaires. Growth characteristics were measured from birth onwards. At 6 years, body fat and insulin levels were measured. Results: Compared to children whose mothers consumed <2 units of caffeine per day during pregnancy (1 unit of caffeine is equivalent to 1 cup of coffee (90 mg caffeine)), those whose mothers consumed ≥6 units of caffeine per day tended to have a lower weight at birth, higher weight gain from birth to 6 years and higher body mass index from 6 months to 6 years. Both children whose mothers consumed 4-5.9 and ≥6 units of caffeine per day during pregnancy tended to have a higher childhood body mass index and total body fat mass. Only children whose mothers consumed ≥6 units of caffeine per day had a higher android/gynoid fat mass ratio. Conclusions: Our results suggest that high levels of maternal caffeine intake during pregnancy are associated with adverse offspring growth patterns and childhood body fat distribution. |
| PDF Link | |
| Reason for Inclusion | I selected this article because it was a population-based birth cohort study that followed mothers and their offspring until age 6 years. It looked directly at the association between maternal caffeine intake during pregnancy and offspring growth pattern, body fat, and insulin levels. It included a large cohort of 7,857 mothers and their offspring. |
| Article #4 | |
| Citation | Chen LW, Murrin CM, Mehegan J, Kelleher CC, Phillips CM; Cross-Generation Cohort Study for the Lifeways. Maternal, but not paternal or grandparental, caffeine intake is associated with childhood obesity and adiposity: The Lifeways Cross-Generation Cohort Study. Am J Clin Nutr. 2019;109(6):1648-1655. doi:10.1093/ajcn/nqz019 |
| Abstract | Background: Maternal caffeine intake is associated with adverse birth outcomes, but its long-term influence on offspring adiposity outcomes is not well studied. Furthermore, few studies have investigated paternal and grandparental caffeine intake in relation to offspring outcomes. Objective: To study the associations between maternal, paternal, and grandparental caffeine intake and offspring childhood adiposity. Design: The core study sample consists of 558 mother-child pairs from the Lifeways Study. Caffeine intake was derived from relevant food items in a self-administered validated food frequency questionnaire in early pregnancy. Children’s body mass index (BMI) and waist circumference (WC) were measured at 5- and 9-y follow-up. Childhood overall and central obesity were defined as age- and sex-specific BMI z-score > International Obesity Task Force cut-off and WC z-score > 90th percentile, respectively. Multiple linear and logistic regressions were used to assess associations. Results: Study mothers had a mean age of 30.8 y and a mean prepregnancy BMI (kg/m2) of 23.7. In adjusted models, maternal caffeine intake was associated with a higher offspring BMI z-score [β (95% CI): 0.13 (0.06, 0.21) for year 5 and 0.17 (0.04, 0.29) for year 9; per 100 mg/d increment in maternal caffeine intake], WC z-score [β (95% CI): 0.09 (0.01, 0.17) for year 5 and 0.19 (0.05, 0.32) for year 9], and a higher risk of offspring overall obesity [OR (95% CI): 1.32 (1.11, 1.57) for year 5 and 1.44 (1.10, 1.88) for year 9] and central obesity [1.28 (1.02, 1.60) for year 5 and 1.62 (1.12, 2.34) for year 9]. The influence was stronger for coffee caffeine than tea caffeine. No consistent associations were observed for paternal and grandparental caffeine intake. Conclusions: Maternal antenatal, but not paternal or grandparental, caffeine intake is associated with higher offspring adiposity and obesity risk at age 5 and 9 y, with stronger associations observed for coffee caffeine. |
| PDF Link | |
| Reason for Inclusion | I selected this article because it was a recent study from 2019 that looked at the associations between maternal caffeine intake and childhood obesity. It consisted of 558 mothers who were followed during pregnancy and then offspring who were followed until 9 years of age. They assessed BMI and waist circumference to assess obesity. |
| Article #5 | |
| Citation | Jin, F., & Qiao, C. (2020). Association of maternal caffeine intake during pregnancy with low birth weight, childhood overweight, and obesity: a meta-analysis of cohort studies. International Journal of Obesity, 45(2), 279–287. doi:10.1038/s41366-020-0617-4 |
| Abstract | Background: Epidemiological studies reported inconsistent results on the associations between maternal caffeine intake during pregnancy and risk of low birth weight (LBW) and childhood overweight and obesity in their offspring. Methods: We conducted a meta-analysis of cohort studies to quantitatively assess these associations. Pertinent studies were identified by searching PubMed and Embase through June 2019. Study-specifics risk estimates were combined using fixed effects models, or random-effects models when significant heterogeneity was detected. Dose-response analysis was modeled by using restricted cubic splines. Results: A total of 15 cohort studies, with 102,347 pregnancy women, was included in the meta-analysis. The pooled relative risk (RR) for LBW was 1.33 (95% CI: 1.12, 1.57) for mothers with the highest compared with the lowest level of caffeine intake during pregnancy, with significant heterogeneity across studies (I 2 = 49.3%, P = 0.032). The pooled RR was 1.07 (95% CI: 1.02, 1.11) for each 100 mg/day increase of caffeine intake. The pooled RR for childhood overweight and obesity was 1.39 (95% CI: 1.15, 1.69) for mothers with the highest compared with the lowest level of caffeine intake during pregnancy. No significant heterogeneity across studies was detected (I 2 = 38.9%, P = 0.179). The pooled RR was 1.31 (95% CI: 1.11, 1.55) for each 100 mg/day increase of caffeine intake. No evidence of publication bias was indicated. Conclusions: Maternal caffeine intake during pregnancy is associated with higher risk of LBW and childhood overweight and obesity. Further studies may focus on investigating the potential mechanisms before the recommendation of complete avoidance of caffeine intake during pregnancy. |
| PDF Link | |
| Reason for Inclusion | I selected this article because it was a meta-analysis of cohort studies to assess the association between maternal caffeine intake during pregnancy and childhood obesity. It included 15 cohort studies with a total of 102,347 pregnant comen, which is a large sample size to compare. The outcomes it looked at included risk of low birth weight, childhood overweight status, and childhood obesity. |
| Article #6 | |
| Citation | Li, D.-K., Ferber, J. R., & Odouli, R. (2014). Maternal caffeine intake during pregnancy and risk of obesity in offspring: a prospective cohort study. International Journal of Obesity, 39(4), 658–664. doi:10.1038/ijo.2014.196 |
| Abstract | Background: In-utero exposures through adverse fetal programming are emerging as an important contributing factor to the epidemic of childhood obesity. This study examines the impact of in-utero exposure to caffeine on the risk of childhood obesity in offspring. Methods: A prospective study of pregnant women with 15 years follow-up of their offspring was conducted to examine the impact of in-utero exposure to caffeine on the risk of childhood obesity. Maternal caffeine intake was prospectively ascertained during pregnancy and outcome measures (body mass index (BMI)) were ascertained from medical charts, with 17 BMI measurements per child, on average, during the follow-up period. Potential confounders including known perinatal risk factors for childhood obesity were adjusted for using the generalized estimating equations model with repeated measurements. Results: After controlling for potential confounders, compared with those without caffeine exposure, in-utero exposure to caffeine overall is associated with 87% increased risk of childhood obesity: odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.12–3.12. This association demonstrated a dose–response relationship: OR = 1.77 (1.05–3.00) for maternal daily caffeine intake o150 mg per day, OR = 2.37 (1.24–4.52) for caffeine intake ⩾150 mg per day during pregnancy, respectively. We also observed a linear relationship: every one unit increase (log10 scale) in the amount of maternal caffeine intake was associated with 23% increased risk of obesity in offspring. The dose–response relationship appears stronger for persistent obesity than for transitory obesity (occasional high BMI), and for girls than for boys. Conclusion: We observed an association of in-utero exposure to caffeine with increased risk of childhood obesity. If this observation is further replicated in other studies, the finding will contribute to the understanding of fetal programming of childhood diseases and development of intervention strategy to prevent childhood obesity. |
| PDF Link | |
| Reason for Inclusion | I selected this article because it was a prospective study of the in-utero exposure of infants to caffeine intake by the mother and the risk of childhood obesity in offspring. It included 1,063 women and examined their caffeine intake during pregnancy. This study, while a smaller sample size, followed its cohort for over 15 years, which I felt was significant enough to include. It looked specifically at how the caffeine intake affected the offspring’s BMI and growth patterns for the next 15 years. |
Summary of the Evidence:
| Author (Date) | Level of Evidence | Sample/Setting(# of subjects/ studies, cohort definition etc. ) | Outcome(s) studied | Key Findings | Limitations and Biases |
| Frayer et al, 2020Caffeine Intake During Pregnancy and Risk of Childhood Obesity: A Systematic Review | Systematic Review | 8 studies evaluating caffeine intake during pregnancy, 34,443 mother/child pairs, children followed on average 6-10 years | Association of maternal caffeine intake during pregnancy and childhood obesity status Overweight status in childhood, altered fat deposition, altered childhood anthropometrics | 5 out of 8 studies found an association between maternal caffeine consumption of >50mg/day and offspring obesity or elevated BMI Caffeine intake as low as 50mg/day during pregnancy increases the risk for childhood obesity in offspring The likelihood of offspring obesity increased as caffeine intake increased Increased caffeine intake during pregnancy was associated with increased risk of overweight children, increased total body weight, and increased risk of central obesity or waist circumference Maternal caffeine intake was associated with an increased childhood total body mass and body fat mass Current recommendations of <200mg/day present a lower risk of offspring obesity, but complete avoidance would eliminate any related risk Future research with large cohort populations is needed to further determine | The consumption of caffeine was measured from food frequency questionnaires and in person interviews, which can lead to self reporting errors Coffee was the main sources of caffeine, but there were other types and sources with varying levels of caffeine depending on preparation |
| Papadopoulou et al, 2018Maternal caffeine intake during pregnancy and childhood growth and overweight: results from a large Norwegian prospective observational cohort study. | Prospective observational cohort study | A total of 50,943 mothers and their children, following the children from 6 weeks to 8 years | Excess infant weight gain in relation to maternal caffeine intake Childhood overweight and obesity status | As prenatal caffeine intake increased from low (<200mg /day) to high (>300mg/day), excess growth in infancy increased from 23% to 29% Children born to those with higher caffeine intake had higher rates of excess growth in infancy There is a positive association between caffeine intake and risk of excess growth, and the growth is linear and applicable up to 8 years With increasing prenatal caffeine exposure, the prevalence of overweight status in offspring increased by 5% at 3 years, 6% at 5 years, and 3% at 8 years Similar results were seen with various caffeine sources – black coffee, black tea, soda drinks Caffeine intake < 300mg/day was still significantly associated with increased risk for excess infant growth and overweight status, even excluding very high caffeine consumers High prenatal caffeine exposure was positively associated with a child’s weight, weight gain velocity, and BMI from the first month onwards Maternal caffeine intake at any level above 50mg/day during pregnancy is associated with higher BMI from ages 1 month to 8 years | There could be confounding or non accounted factors related to an overall unhealthy lifestyle that explain the findings, due to a possible association with high caffeine intake and unhealthy lifestyle Missing body size measurements of participants over time, which was handled with a growth model Dietary data was self-reported |
| Voerman et al, 2016 Maternal caffeine intake during pregnancy, early growth, and body fat distribution at school age | Population-based birth cohort | Cohort of 7,857 mothers and their offspring, following the cohort until age 6 years | Association of high levels of maternal caffeine intake during pregnancy with adverse offspring growth patterns and childhood body fat distribution Effect of maternal caffeine intake on childhood insulin and c-peptide levels | High levels of maternal caffeine intake during pregnancy are associated with adverse offspring growth patterns and childhood body fat distribution Mothers who consumed > 540mg of caffeine per day had shorter children than those who consumed < 2 units per day, but these differences decreased slightly over time Children of mothers who consumed > 540 mg of caffeine caffeine per day during pregnancy had lower birth weights and higher weight gain from birth to 72 months BMI was higher from 6 months to 72 months in children whose mothers consumed > 540mg of caffeine per day during pregnancy Higher intake of caffeine per day was associated with higher childhood BMI and childhood total body fat mass | 30% of eligible participants were not participating in follow up measurements at 6 years, which led to loss of follow up Maternal caffeine intake was self-reported, which could be underreportedCaffeine intake was assessed from coffee and tea only, and not other sources such as soft drinks, chocolate, and medications |
| Chen et al, 2019 Maternal, but not paternal or grandparental, caffeine intake is associated with childhood obesity and adiposity: The Lifeways Cross-Generation Cohort Study. | Cross-generation observational cohort study | Observational cohort study of 558 mother-child pairs with 5 year and 9 year follow up Assessments of BMI and waist circumference | Determine associations between maternal, paternal, and grandparental caffeine intake and offspring childhood adiposity | Maternal caffeine intake was associated with a higher sex and age-specific BMI score from ages 5-9 years There was a statistically significant association between maternal caffeine intake > 200mg/day and increased BMI. A 100mg/day increment in maternal caffeine intake was asssociated with higher risk of offspring’s overall overweight and obese status Caffeine from coffee but not tea was associated with offspring overall overweight and obesity Maternal BMI and child gender did not modify the relation between maternal caffeine intake and offspring adiposity Only maternal, not paternal or grandparental intake of caffeine, was associated with higher offspring adiposity | Caffeine intake and sources were self-reported by mothers in the study Energy drinks were not considered in total caffeine intake Various intakes over the course of pregnancy – some mothers consuming more caffeine |
| Jin et al, 2020Association of Maternal Caffeine Intake During Pregnancy with Low Birth Weight, Childhood Overweight, and Obesity: A Meta-Analysis of Cohort Studies. | Meta-analysis of cohort studies | 15 cohort studies including a total of 102,347 pregnant women and their offspring | Evaluate the effects of maternal caffeine exposure on the abnormal body weight of their offspring from birth to childhood Two most reported outcomes were low birth weight (LBW) and childhood overweight/obesity | Maternal caffeine intake during pregnancy was associated with higher risk of LBW and childhood overweight and obesityIncreased maternal caffeine intake led to increased rates of obesityThere was a 3% increase in risk in LBW for every 100mg of caffeine consumed per day during pregnancy 39% risk of childhood overweight and obesity with higher maternal caffeine intake during pregnancy Maternal caffeine intake was associated with overall increased risk of obesity from ages 2-15 years | Residual confounding variables could distort the associationSignificant heterogeneity among studies results, some including caffeine sources of soda, energy drinks, chocolate, black teaLength of follow up and study size varied from study to study |
| Li et al, 2014Maternal caffeine intake during pregnancy and risk of obesity in offspring: a prospective cohort study | Prospective cohort study | 1,063 pregnant women in San Francisco area, followed for 15 years | Impact of in-utero exposure to caffeine on the risk of childhood obesity in offspring | In-utero exposure to caffeine was associated with an 87% increased risk of childhood obesity Linear relationship – for every one unit increase in caffeine intake, there was a 23% increased risk of obesity in offspring Compared with no caffeine intake, maternal caffeine intake overall was associated with an 87% increased risk of obesity Maternal caffeine intake > 150mg per day was associated with more than twice the risk of childhood obesity The association between maternal caffeine intake and obesity risk in offspring did not appear to be source specific Adjustment for additional factors like education level, gestational diabetes, fruit and vegetable intake of children, tv watching, and exercise of children did not change results | Small area of San Francisco made up the whole cohort, which could influence the demographics of the studyThe study had caffeine intake that was self-reported, which could influence the outcomes |
Conclusion(s):
Frayer et al. – The risk of childhood overweight or obesity was associated with caffeine consumption at 50 mg/day during pregnancy with a stronger association at intakes ≥300 mg/day and higher.
Papadopoulou et al. – Maternal caffeine intake during pregnancy and childhood growth and overweight: results from a large Norwegian prospective observational cohort study.
Voerman et al. – Compared to children whose mothers consumed <2 units of caffeine per day during pregnancy (1 unit of caffeine is equivalent to 1 cup of coffee (90 mg caffeine)), those whose mothers consumed ≥6 units of caffeine per day tended to have a lower weight at birth, higher weight gain from birth to 6 years and higher body mass index from 6 months to 6 years.
Chen et al. – Maternal antenatal, but not paternal or grandparental, caffeine intake is associated with higher offspring adiposity and obesity risk at age 5 and 9 y, with stronger associations observed for coffee caffeine.
Jin et al. – Maternal caffeine intake during pregnancy is associated with higher risk of LBW and childhood overweight and obesity.
Li et al. – Maternal caffeine intake during pregnancy was associated with an 87% increased risk of childhood obesity in offspring compared to no maternal caffeine intake
Overall, all studies showed that an increased consumption of caffeine during pregnancy increased the risk of childhood obesity in offspring. All studies recommended further long term research to evaluate the exact effects and outcomes dependent on the level of caffeine consumption.
Clinical Bottom Line:
The clinical bottom line from these articles is that maternal caffeine intake is associated with an increased risk of childhood obesity and overweight status. Various studies followed maternal caffeine intake through pregnancy, and then followed offspring growth status afterwards. All the studies listed above showed that there was a statistically significant association between increased maternal caffeine intake and increased risk of offspring obesity. From these studies, it appears that as the level of caffeine intake increases, so does the risk of childhood obesity. High levels of caffeine intake, above 200-300mg/day, have the highest risk of leading to obesity in offspring. High prenatal caffeine exposure affects a child’s weight, weight gain velocity, and BMI from infancy to childhood. While the biggest association was seen with high levels of caffeine intake, it appears that any level can have some impact on the risk for children. With these outcomes in mind, caffeine avoidance during pregnancy is the best recommendation that can be made to patients, as that effectively eliminates the risk. In patients who choose to continue to drink coffee, limiting their intake to < 200mg/day is recommended to decrease the likelihood of childhood obesity risk.
Weight of Evidence:
Jin et al. Association of maternal caffeine intake during pregnancy with low birth weight, childhood overweight, and obesity: a meta-analysis of cohort studies. (2020)
I weighted this article first because it is a meta-analysis of cohort studies. It includes 15 cohort studies with a total of 102,347 pregnant women. It looked at the association between maternal caffeine intake during pregnancy and birth weight, childhood weight, and the risk of overweight/obesity. It is a very recent study, published in 2020, and takes into account previous recommendations and research within its evaluation. The very large sample size provides sufficient statistical power to quantitatively assess the relationship between maternal caffeine intake and risk of childhood overweight and obesity. Additionally, including only cohort studies limits the risk of selection and recall bias.
Frayer et al. Caffeine Intake During Pregnancy and Risk of Childhood Obesity: A Systematic Review. (2020).
I weighted this article second because it is a systematic review focused on the association between caffeine consumption during pregnancy and overweight or obesity in offspring. It evaluated 8 studies, which were prospective cohort populations. Some of the studies measured infants at 6 months as the endpoint, while others went to 15 years. The sample size was 34,443. It looked specifically at the intake of caffeine and the effect on childhood BMI and obesity, but the ways caffeine content was measured differently in each study. Five of the eight studies found an association between maternal caffeine consumption and offspring obesity. The strength of this study is the large sample size from various countries, which allows for a broader conclusion applicable across demographics.
Papadopoulou et al. Maternal caffeine intake during pregnancy and childhood growth and overweight: results from a large Norwegian prospective observational cohort study. (2018).
I weighted this article third because it is a prospective observational cohort study, rather than a large meta-analysis. It is based in Norway and limited to Norwegian participants, which makes it less applicable across demographics. It included 50,943 mothers which is quite a large sample size, and followed participants from birth over the span of eight years. It looked specifically at the outcome of maternal caffeine intake and childhood growth.
Voerman et al. Maternal caffeine intake during pregnancy, early growth and body fat distribution at school-age. The Generation R Study. (2016)
I weighted this article fourth because it is a population-based birth cohort among 7,857 mothers and children. It assessed maternal caffeine intake during pregnancy, but was conducted mostly with questionnaires, which I feel limits the data. It followed the children from birth to six years, which is a shorter length of time than other studies.It did directly assess maternal caffeine intake during pregnancy, as well as how that affected childhood growth, body fat distribution, insulin and c-peptide levels. However, it was focused in the Netherlands specifically, not as broad reaching as other studies.
Li – Maternal caffeine intake during pregnancy and risk of obesity in offspring: a prospective cohort study
I weighted this article fifth because it was a prospective cohort study. It looked at the outcome of maternal caffeine intake during pregnancy and risk of obesity in offspring. The sample size was only 1,063 but it had 15 years of follow up, which I think is notable. Each child had an average of 17 BMI measurements during the follow up period, and they adjusted for perinatal risk factors for childhood obesity.
Chen et al. Maternal, but not paternal or grandparental, caffeine intake is associated with childhood obesity and adiposity: The Lifeways Cross-Generation Cohort Study. (2019).
I weighted this article sixth because it was a cross-generation prospective cohort study, which looked at the effects of grandparental as well as paternal and maternal caffeine intake on offspring. However, this is a little more broad than my focused outcome. The sample size was only 558 mother-child pairs. The caffeine intake was from a food frequency questionnaire, and children were measured at five and nine year follow ups.
Overall the evidence presented in the above studies is strong. The highest weighted studies meta-analyses or systematic reviews, and those that were not were prospective studies that observed the cohorts over time, which makes the most sense for assessing a correlation or potential causation. All of the studies looked directly at how maternal caffeine intake during pregnancy affected the risk of childhood obesity or overweight status, usually through BMI or growth measurements. The sample size of the majority of the studies was very large, and the ones with smaller sample size had longer follow up or multiple outcomes assessed.
Magnitude of Effects:
Frayer et al. Caffeine Intake During Pregnancy and Risk of Childhood Obesity: A Systematic Review. (2020).
The studies evaluated their data utilizing linear regression models of which the results were recorded by a standard deviation score with a 95% confidence interval (95% CI) and odds ratios (OR). Odds ratio with a 95% CI was utilized to compare mothers who consumed less amounts of caffeine (<50 mg/day,15 <150 mg/day,24 and <180 mg/day13) to those who consumed more (>50 mg/day,15≥150 mg/day,24 and ≥180 mg/day13). P-value or P for trend of <0.05 was used to establish significance for all of the studies except Barr and Streissguth.27 The study that utilized serum paraxanthine28 also evaluated the difference of BMI scores with serum paraxanthine levels using a Risk Ratio and 95% CI. Since each study presented different assessments of mothers’ caffeine sources during pregnancy, as well as varying anthropometrics and follow-up times, a meta-analysis was not possible and therefore a systematic review ensued.
Papadopoulou et al. Maternal caffeine intake during pregnancy and childhood growth and overweight: results from a large Norwegian prospective observational cohort study. (2018).
Compared with pregnant women with low caffeine intake (<50mg/day, 46%), women with average (50–199mg/day, 44%), high (≥200–299mg/day, 7%) and very high (≥300mg/day, 3%) caffeine intakes had an increased risk of their child experiencing excess growth in infancy, after adjustment for confounders (OR=1.15, 95% CI 1.09 to 1.22, OR=1.30, 95%CI 1.16 to 1.45, OR=1.66, 95%CI 1.42 to 1.93, respectively). In utero exposure to any caffeine was associated with higher risk of overweight at age 3 years and 5 years, while the association persisted at 8 years, only for very high exposures. Any caffeine intake was associated with increased body mass index from infancy to childhood. Children prenatally exposed to caffeine intake >200mg/ day had consistently higher weight. Very high caffeine exposures were associated with higher weight gain velocity from infancy to age 8 years.
Voerman et al. Maternal caffeine intake during pregnancy, early growth and body fat distribution at school-age. The Generation R Study. (2016)
Compared to children whose mothers consumed <2 units of caffeine per day during their pregnancy, both those whose mothers consumed 4-5.9 units and ≥6 units of caffeine per day tended to have a higher childhood body mass index (differences: 0.09 Standard deviation score (SDS) (95% Confidence Interval (CI): -0.01, 0.19) and 0.16 SDS (95% CI: -0.03, 0.36), respectively) and a higher childhood total body fat mass (differences: 0.10 SDS (95% CI: 0.01, 0.20) and 0.18 SDS (95% CI: -0.01, 0.37), respectively) (Table 2). Only children whose mothers consumed ≥6 units of caffeine per day during their pregnancy had a higher childhood android/gynoid fat mass ratio (difference: 0.27 SDS (95% CI: 0.05, 0.49)). Similar tendencies were present when we combined the upper two maternal caffeine intake categories into one category (results not shown). Supporting Information Table S5 shows similar results from the basic models. Supporting Information Table S6 shows that as compared to children whose mothers consumed <2 units of caffeine per day during pregnancy, those whose mothers consumed ≥6 units of caffeine per day tended to have higher risks of childhood overweight (Odds Ratio (OR): 1.25 (95% CI: 0.68, 2.30) in the fully adjusted model
Chen et al. Maternal, but not paternal or grandparental, caffeine intake is associated with childhood obesity and adiposity: The Lifeways Cross-Generation Cohort Study. (2019).
Study mothers had a mean age of 30.8 y and a mean prepregnancy BMI (kg/m2) of 23.7. In adjusted models, maternal caffeine intake was associated with a higher offspring BMI z-score [β (95% CI): 0.13 (0.06, 0.21) for year 5 and 0.17 (0.04, 0.29) for year 9; per 100 mg/d increment in maternal caffeine intake], WC zscore [β (95% CI): 0.09 (0.01, 0.17) for year 5 and 0.19 (0.05, 0.32) for year 9], and a higher risk of offspring overall obesity [OR (95% CI): 1.32 (1.11, 1.57) for year 5 and 1.44 (1.10, 1.88) for year 9] and central obesity [1.28 (1.02, 1.60) for year 5 and 1.62 (1.12, 2.34) for year 9].
Jin et al. Association of maternal caffeine intake during pregnancy with low birth weight, childhood overweight, and obesity: a meta-analysis of cohort studies. (2020)
The pooled relative risk (RR) for LBW was 1.33 (95% CI: 1.12, 1.57) for mothers with the highest compared with the lowest level of caffeine intake during pregnancy, with significant heterogeneity across studies (I2 = 49.3%, P = 0.032). The pooled RR was 1.07
(95% CI: 1.02, 1.11) for each 100 mg/day increase of caffeine intake. The pooled RR for childhood overweight and obesity was 1.39 (95% CI: 1.15, 1.69) for mothers with the highest compared with the lowest level of caffeine intake during pregnancy. No significant heterogeneity across studies was detected (I2 = 38.9%, P = 0.179). The pooled RR was 1.31 (95% CI: 1.11, 1.55) for each 100 mg/day increase of caffeine intake. No evidence of publication bias was indicated.
Li et al. Maternal caffeine intake during pregnancy and risk of obesity in offspring: a prospective cohort study. (2014).
After controlling for potential confounders, compared with those without caffeine exposure, in-utero exposure to caffeine overall is associated with 87% increased risk of childhood obesity: odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.12–3.12. This association demonstrated a dose–response relationship: OR = 1.77 (1.05–3.00) for maternal daily caffeine intake o150 mg per day, OR = 2.37 (1.24–4.52) for caffeine intake ⩾150 mg per day during pregnancy, respectively. We also observed a linear relationship: every one unit increase (log10 scale) in the amount of maternal caffeine intake was associated with 23% increased risk of obesity in offspring. The dose–response relationship appears stronger for persistent obesity than for transitory obesity (occasional high BMI), and for girls than for boys.
Clinical Significance:
The significance of this research is that there is clearly an association between caffeine consumption during pregnancy and risk of childhood obesity or overweight status. While it has previously been shown that maternal caffeine intake increases the risk of low birth weight and intrauterine growth restrictions, the long term effects of caffeine intake during pregnancy are not as closely studied. However, the results of these studies show that there is a clear association between increased caffeine intake and increased risk of obesity. Granted, there could be many confounding variables at play as well, but even with controlling or eliminating as many as possible, there is still a significantly increased risk. This is clinically significant as many mothers choose to drink coffee during pregnancy. The classic recommendation is that one cup of coffee a day during pregnancy is acceptable and has a low risk for the fetus. However, clearly more research needs to be done to look at how various levels of caffeine intake can have an effect, because so far these studies show that even some caffeine intake increases the risk of obesity.
Other Considerations:
A consideration for the future is comparing different amounts of caffeine and evaluating the outcome. Would smaller amounts still have the exact same statistically significant results? Another thing worth looking at is how the source type influences these outcomes. While the majority of people get caffeine from coffee and tea, there are other sources that are worth considering. For example, within my own religious culture, coffee and tea are avoided but many people drink sodas that contain caffeine. It would be interesting to see if the outcomes remain the same with different sources.
