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Study Title and Description

Caffeine intake and small-for-gestational-age birth: modifying effects of xenobiotic-metabolising genes and smoking.



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?
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Primary Publication Information
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TitleData
Title Caffeine intake and small-for-gestational-age birth: modifying effects of xenobiotic-metabolising genes and smoking.
Author C Infante-Rivard,
Country
Year 2007
Numbers

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Reproductive Toxicity - Design Details
Arms
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Design Details
Question... Follow Up Answer Follow-up Answer
Refid 17564586
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What outcome is being evaluated in this paper? Reproductive and Development
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What is the objective of the study (as reported by the authors)? The relationship between caffeine consumption and small-for-gestational-age (SGA) birth remains uncertain. However, factors that can influence caffeine metabolism, such as genetic polymorphisms, have not been considered, while other similar factors such as smoking and ethnicity have not always been fully accounted for in the interpretation of results. We carried out a study on the relationship between caffeine intake and small-for-gestational-age (SGA) birth, taking into account the potential modifying effects of smoking and genetic polymorphisms in CYP1A2 and CYP2E1.
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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) A case–control study was carried out comprising 493 cases and 472 controls. Cases were newborns whose birthweight was below the 10th percentile according to gestational age and sex, based on national norms, and controls were at or above the 10th percentile (babies born after 24 weeks). Caffeine consumption from beverages was estimated for each pregnancy trimester in face-to-face interview in the hospital within 2 days of delivery. The following conversion factors from cups to mg were used, adapted from Barone and Roberts: one cup of caffeinated coffee was assumed to contain 106 mg of caffeine and a cup of decaffeinated coffee, 3 mg; a cup of caffeinated tea was assigned 35 mg of caffeine, while a cup of decaffeinated tea was assumed to contain zero; a caffeinated cola was assigned 35 mg of caffeine and decaffeinated cola, zero.Maternal and newborn variants in the CYP1A2 and CYP2E1 genes involved in the metabolism of caffeine were determined using PCR. ORs and 95% CIs were estimated using unconditional logistic regression analysis. To analyse the role of caffeine consumption in SGA as an outcome, we first used a model adjusting for race as a matching factor, gestational age and sex having been accounted for in the definition of SGA (i.e. adjusting or not for gestational age and sex gives identical results); a second model was used where we adjusted for race, mother’s pre-pregnancy body mass index, primiparity, maternal daily cigarette smoking (none or any quantity), and reported nausea by trimester. Caffeine consumption was defined in turn as either a dichotomy with cutpoint at <300 mg or as a continuous variable.
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How many outcome-specific endpoints are evaluated? 1
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What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately) SGA/IUGR
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List additional health endpoints (separately).
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List additional health endpoints (separately)
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Notes SGA defined as born after 24 weeks below the 10th percentile according to gestational age and sex.
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Clinical Clinical
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Physiological
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Other
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What is the study design? Case-Control
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Randomized or Non-Randomized?
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What were the diagnostics or methods used to measure the outcome? Objective
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Optional: Name of Method or short description Not described - assumed to be standard hospital practice
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Caffeine (general) Caffeine (general)
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Coffee Coffee
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Chocolate
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Energy drinks
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Gum
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Medicine/Supplement
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Soda Soda
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Tea Tea
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Measured
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Self-report Self-report
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Children
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Adolescents
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Adults
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Pregnant Women Pregnant Women
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What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.) <300 mg/day vs. >/= 300 mg/day caffeine
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What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models.  Copy from methods) To analyse the role of caffeine consumption in SGA as an outcome, we first used a model adjusting for race as a matching factor, gestational age and sex having been accounted for in the definition of SGA (i.e. adjusting or not for gestational age and sex gives identical results); a second model was used where we adjusted for race, mother’s pre-pregnancy body mass index, primiparity, maternal daily cigarette smoking (none or any quantity), and reported nausea by trimester.
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Provide a general description of results (as reported by the authors). Contrasting consumption by trimester of >/=300 mg/day with a lower level, or using caffeine as a continuous measure, while adjusting for smoking and nausea, showed no increased risk for SGA (REVIEWR NOTE: OR data for overall population not shown, only by smoking subgroup). However, when stratifying for cigarette smoking, caffeine odds ratios (for the continuous and dichotomous measures) in the first trimester were statistically heterogeneous, suggesting a greater risk among non-smokers. Using birthweight as the outcome and caffeine as a continuous measure, a small 38 g [95% confidence interval -68, -8] decrement for every 100 mg of daily caffeine was observed in the third trimester. Although reductions in birthweight were apparently greater in nonsmokers than in smokers, these differences were not statistically significant. The studied polymorphisms did not modify the effect of caffeine.
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Did the authors perform a dose-response analysis (or trend/related analysis)? No
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What were the authors's observations re: trend analysis?
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What were the author's conclusions? Caffeine consumption is unlikely to be a major risk factor for SGA or low birthweight in pregnant women.
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What were the sources of funding? The project was funded by grants from the Canadian Institutes of Health Research.
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What conflicts of interest were reported? The author holds a James McGill Professorship (Canada Research Chair).
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Does the exposure (dose) need to be standardized to the SR? No
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Provide calculations/conversions for the exposure based on the decision tree in the guide (for all endpoints/exposure levels of interest).
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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.  SGA NOAEL = >/=300 mg/day
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Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot. Although the authors state that intake >/= 300 mg/day adjusted for smoking and nausea was not associated - the analyses/data are not shown (i.e., no OR to report). The analyses by smoking status are provided and all ORs are 1-2 for non-smokers and <1 for smokers, but none were significant.
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What is the importance of the study with respect to the adverseness of the outcome? Important
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