Study Title and Description
Effect of reducing caffeine intake on birth weight and length of gestation: randomised controlled trial.
Key Questions Addressed
|1||For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on reproductive and developmental outcomes?|
Primary Publication Information
|Title||Effect of reducing caffeine intake on birth weight and length of gestation: randomised controlled trial.|
|Author||BH Bech,C Obel,TB Henriksen,J Olsen,|
Secondary Publication Information
There are currently no secondary publications defined for this study.
Extraction Form: Reproductive Toxicity - Design Details
No arms have been defined in this extraction form.
|Question... Follow Up||Answer||Follow-up Answer|
|What outcome is being evaluated in this paper?||Reproductive and Development|
|What is the objective of the study (as reported by the authors)?||Women with a high caffeine intake during pregnancy differ in many ways from women with a low or no caffeine intake. They smoke more, have a higher alcohol intake, and have attained a lower level of education.Despite attempts to control for these factors there are limits as to how much can be controlled in non-experimental studies. We carried out a randomized double blind trial to estimate the effect of reducing caffeine intake on birth weight and length of gestation.|
|Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods)||Randomized double blind controlled trial of 1207 pregnant women drinking at least three cups of coffee a day, recruited before 20 weeks’ gestation. Participants in the cohort completed a telephone interview around 12 weeks of pregnancy. The women were randomized to receive caffeinated instant coffee or decaffeinated instant coffee. We bought the coffee from the manufacturer, in identical boxes without labels. The women were allocated to either group by a computer generated randomization schedule and assigned serial numbers in balanced blocks of six. Staff not in contact with participants and endpoint data applied a label with the serial number to each of the boxes according to the randomization schedule. After the project coordinator (BHB) had received the consent form (at about 18 weeks’ gestation) she posted six boxes of coffee to each participant, who were registered with the serial number applied to the box. BHB and the participants were blinded to the type of coffee, and the blinding was broken only at the end of the data analyses. The women could request as much coffee as they needed free of charge. We asked the women to replace their usual coffee with that provided, but we did not advise them on how much to drink or ask them to avoid regular coffee offered by others or intake of other caffeinated beverages such as tea, cocoa, or cola. The women were interviewed throughout pregnancy to obtain data on daily consumption of the study coffee, other caffeinated beverages (coffee, tea, cola, or cocoa), and smoking status. The interviews were scheduled at gestational weeks 20, 25, and 34 and at four weeks after the expected date of delivery. Average estimates of caffeine per cup were: caffeinated study coffee 65 mg (according to manufacturer), decaffeinated study coffee 0 mg; other coffee 100 mg; tea 50 mg; drinking chocolate and cola per glass (2 dl) 5 mg and 20 mg.26 Data were not available on size of cups but were available on whether women used regular sized cups or mugs; a mug of coffee was classed as two cups. In the final interview we asked the women to guess (or state "don’t know") which type of coffee they had received. Outcomes were obtained from the Danish national birth register. To produce more valid estimates we adjusted for several potential confounders selected a priori and recorded at baseline; gestational age (in the analysis of birth weight) and prepregnancy body mass index, parity, and smoking status. All reported P values are two sided, and we defined statistical significance at the 5% level. If the standard deviation of birth weight was set to 500 g we calculated that a sample size of 800 women would give 80% power to detect a difference in birth weight of at least 100 g at a 5% two sided significance level.|
|How many outcome-specific endpoints are evaluated?||2|
|What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately)||Birth weight|
|List additional health endpoints (separately).|
|List additional health endpoints (separately)|
|Notes||Secondary endpoints included: birth length, ponderal index, head circumference, abdominal circumference, placenta weight - p values were not provided for these|
|What is the study design?||Controlled Trial|
|Randomized or Non-Randomized?||RCT|
|What were the diagnostics or methods used to measure the outcome?||Objective|
|Optional: Name of Method or short description||Birth registry|
|Caffeine (general)||Caffeine (general)|
|Pregnant Women||Pregnant Women|
|What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.)||Low caffeine 117 mg/day vs. high caffeine 317 mg/day - note: these values are the median, the mean difference between high and low was stated to be 183 mg/day|
|What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models. Copy from methods)||gestational age (in the analysis of birth weight) and prepregnancy body mass index, parity, and smoking status|
|Provide a general description of results (as reported by the authors).||568 women were randomized to caffeinated instant coffee and 629 to decaffeinated instant coffee. Using the Wilcoxon rank sum test no significant difference was found in gestational age between the groups (table 3; P=0.48). After adjustment for determinants of birth weight at baseline the mean difference in birth weight between babies of women randomized to decaffeinated minus caffeinated coffee was 16 g (95% confidence interval −40 to 73; P=0.57). The difference in mean birth weight and length of gestation between the groups was not modified by coffee consumption at study entry or by compliance with the protocol. In the caffeinated and decaffeinated groups, respectively, 4.2% (23/552) and 5.2% (31/601) of infants were born preterm, 4.5% (25/552) and 4.7% (28/598) were small for gestational age, and 0.8% (4/527) and 1.0% (6/578) had an Apgar score of less than 7 after five minutes. None of these differences was statistically significant. In the caffeinated group 35% (191/552) of women guessed the type of coffee they received compared with 49% (296/601) in the decaffeinated group; 20% (123/601) in the decaffeinated group and 22% (121/ 552) in the caffeinated group could not guess. This difference in guessing was statistically significant.|
|Did the authors perform a dose-response analysis (or trend/related analysis)?||No|
|What were the authors's observations re: trend analysis?|
|What were the author's conclusions?||Providing decaffeinated coffee to women who drank three cups of coffee or more a day in early pregnancy had no effect on birth weight or length of gestation|
|What were the sources of funding?||The project is supported by a grant from the Health Insurance Foundation (No 1105-93 and 11099-96). The Danish National Research Foundation established the Danish Epidemiology Science Centre that initiated and created the Danish national birth cohort. The birth cohort is furthermore a result of a major grant from this foundation. Additional support for the birth cohort was obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, and the Augustinus Foundation. Nestle´ was not involved in the design, analyses, or writing of this paper.|
|What conflicts of interest were reported?||None declared|
|Does the exposure (dose) need to be standardized to the SR?||No|
|Provide calculations/conversions for the exposure based on the decision tree in the guide (for all endpoints/exposure levels of interest).|
|List all the endpoint(s) followed by the dose (mg) which will be used in comparison to Nawrot. Characterize value as LOAEL/NOAEL, etc. if possible.||NOAEL = 317 mg/day for birth weight and length of gestation|
|Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot.||The NOAEL was selected based on the 2 exposure groups - low caffeine 117 mg/day vs. high caffeine 317 mg/day - note: these values are the median, the mean difference between high and low was stated to be 183 mg/day. Average estimates of caffeine per cup were: caffeinated study coffee 65 mg (according to manufacturer), decaffeinated study coffee 0 mg; other coffee 100 mg; tea 50 mg; drinking chocolate and cola per glass (2 dl) 5 mg and 20 mg.26 Data were not available on size of cups but were available on whether women used regular sized cups or mugs; a mug of coffee was classed as two cups. Other endpoints were not included as they were secondary and did not have p values reported.|
|What is the importance of the study with respect to the adverseness of the outcome?||Critcal|
No baseline characteristics have been defined for this extraction form.
Results & Comparisons
No Results found.
|Arm or Total||Title||Description||Comments|
No quality dimensions were specified.
No quality rating data was found.