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Study Title and Description

Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis.



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 Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis.
Author LW Chen,Y Wu,N Neelakantan,MF Chong,A Pan,RM van Dam,
Country
Year 2014
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 25238871
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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)? As many women consume caffeine-containing food and beverages during pregnancy, the possible harmful effects of caffeine intake on fetal and birth outcomes warrant evaluation. A number of studies have examined the relationship of maternal caffeine intake with low birth weight with mixed results [15,16]. Therefore, we systematically reviewed the available prospective epidemiological studies and conducted a meta-analysis on the association of maternal caffeine intake during pregnancy with risk of low birth weight and related outcomes, such as small for gestational age (SGA) and intrauterine growth restriction (IUGR).
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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) Meta-analysis was conducted and reported in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline. Potential articles were identified by searching MEDLINE and SCOPUS/EMBASE databases through 17 July 2013. The search was based on combinations of synonyms for caffeine (including its chemical name, coffee and tea) and birth weight (including low birth weight, SGA and IUGR). Two authors independently extracted information on study design, participant characteristics and estimates of associations. Low birth weight was defined as birth weight less than 2,500 g and SGA was defined as birth weight less than the 10th percentile for gestational age. IUGR is officially defined as estimated fetal weight less than the 10th percentile for gestational age, but the definition used in the included studies was based on birth weight (thus similar to SGA). Birth weight difference was defined as the difference in birth weight in the exposed (caffeine consumers) and unexposed (non- or very light- caffeine consumers) groups. Random-effects models were used to derive the summary relative risks (RRs) and corresponding 95% confidence intervals (CIs). To combine the risk estimates from different categories in different studies, we assigned the median value for each category of caffeine intake. When lower and upper boundaries were presented for the category, we assigned the midpoint as an estimate of the median caffeine intake. We used the results for average caffeine intake during the whole pregnancy period if available. Dose–response relationships were assessed using generalized least-squares trend estimation
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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) Birth weight, 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 Low birth weight was defined as birth weight less than 2,500 g and SGA was defined as birth weight less than the 10th percentile for gestational age. IUGR is officially defined as estimated fetal weight less than the 10th percentile for gestational age, but the definition used in the included studies was based on birth weight (thus similar to SGA).
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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? Meta-analysis
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Randomized or Non-Randomized?
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What were the diagnostics or methods used to measure the outcome? Subjective
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Optional: Name of Method or short description
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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
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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.) Caffeine mg/day: no/very low; 50-149, 150-349, >/=350
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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) Study quality assessment was done by considering characteristics such as study design, number of cases and participants, method of exposure assessment and adjustment of confounders.
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Provide a general description of results (as reported by the authors). In our meta-analysis, we included 13 prospective studies: 9 with low birth weight as a binary outcome variable (90,747 participants and 6,303 cases) and 6 with birth weight as a continuous outcome variable (10,015 participants; 2 studies reported both types of outcomes). The summary RR was 1.13 (95% CI 1.06 to 1.21) for low caffeine intake (50 to 149 mg/day), 1.38 (95% CI 1.18 to 1.62) for moderate caffeine intake (150 to 349 mg/day) and 1.60 (95% CI 1.24 to 2.08) for high caffeine intake (≥ 350 mg/day), as compared with the reference category with no or very low caffeine intake. The heterogeneity in study results was low to moderate: I2 = 0.0% for low caffeine intake, 31.9% for moderate caffeine intake and 65.8% for high caffeine intake. Regarding dose– response, because there was no evidence of departure from linearity (P = 0.89), we assumed a linear relationship. The summary RR was 1.13 (95% CI 1.06 to 1.21; Table 2) per 100-mg/day (equivalent to around one cup of coffee) and 1.45 (95% CI 1.20 to 1.76) per 300-mg/day increment of maternal caffeine intake. We also conducted a meta-analysis of studies of caffeine intake and birth weight as a continuous outcome variable. As compared with the reference group with no or very low caffeine intake, birth weight was 9 g lower in the low caffeine intake group (95% CI − 16 to 35), 33 g lower in the moderate caffeine intake group (95% CI 4 to 63), and 69 g lower in the high caffeine intake group (95% CI 35 to 102).
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Did the authors perform a dose-response analysis (or trend/related analysis)? Yes
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What were the authors's observations re: trend analysis? Regarding dose– response, because there was no evidence of departure from linearity (P = 0.89), we assumed a linear relationship.
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What were the author's conclusions? The findings from this meta-analysis of prospective studies suggest that maternal caffeine intake is associated with a higher risk of delivering an infant with low birth weight. Low caffeine intake (50 to 149 mg/day) was associated with a 13%, moderate caffeine intake (150 to 349 mg/day) with a 38%, and high caffeine intake (≥350 mg/day) with a 60% higher risk of low birth weight as compared with very low or no caffeine intake. These results suggest a graded relationship between caffeine intake and low birth weight. In a dose–response analysis, each 100-mg/day increment in maternal caffeine intake (about one cup of coffee) was associated with a 13% higher risk for low birth weight. The association persisted across strata defined by various study and participant characteristics.
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What were the sources of funding? The project was supported by Saw Swee Hock School of Public Health, National University of Singapore, Singapore. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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What conflicts of interest were reported? The authors declare that they have no competing interests.
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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.  Low birth weight/SGA/IUGR (combined): LOAEL = 50-149 mg/day
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Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot. RR was 1.13 (95% CI 1.06 to 1.21) for low caffeine intake (50 to 149 mg/day), 1.38 (95% CI 1.18 to 1.62) for moderate caffeine intake (150 to 349 mg/day) and 1.60 (95% CI 1.24 to 2.08) for high caffeine intake (≥ 350 mg/day), as compared with the reference category with no or very low caffeine intake.
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What is the importance of the study with respect to the adverseness of the outcome? Critcal
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