Study Title and Description
Coffee consumption during pregnancy and the risk of hyperkinetic disorder and ADHD: a prospective cohort study.
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||Coffee consumption during pregnancy and the risk of hyperkinetic disorder and ADHD: a prospective cohort study.|
|Author||KM Linnet,K Wisborg,NJ Secher,PH Thomsen,C Obel,S Dalsgaard,TB Henriksen,|
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)?||The aim of this study was to explore whether intrauterine exposure to coffee increases the risk of clinically verified hyperkinetic disorder and ADHD.|
|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 cohort study with prospectively collected data from the Aarhus Birth Cohort, Denmark. We included 24,068 singletons delivered between 1990 and 1998. Linkage was performed with three Danish longitudinal registers: The Danish Psychiatric Central Register, The Integrated Database for Labour Market Research and The Danish Civil Registration System. We identified 88 children with hyperkinetic disorder and ADHD. Information about coffee consumption during pregnancy was obtained at 16 weeks of gestation from self-administrated questionnaires. Based on hypotheses from experimental animal studies, we categorized coffee into four groups (0, 1–3, 4–9 and 10 or more cups of coffee per day). We further explored the effect of caffeine from tea, chocolate and cola as well as that from coffee. One cup of coffee corresponds to 100 mg of caffeine, one cup of tea or chocolate to 50 mg and one bottle of cola (25 cl) to 50 mg of caffeine (13). Caffeine intake was categorized into less than 100 mg, 100–399 mg, 400–999 mg and 1000 mg or more per day. The associations between intrauterine exposure to coffee and the risk of hyperkinetic disorder and ADHD were analyzed by Cox regression analysis and calculated as hazard ratios but expressed as risk ratios (RR) with 95% confidence intervals (CI).|
|How many outcome-specific endpoints are evaluated?||1|
|What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately)||hyperkinetic disorder and ADHD|
|List additional health endpoints (separately).|
|List additional health endpoints (separately)|
|Notes||Analysis performed on both disorders combined|
|What is the study design?||Cohort|
|Randomized or Non-Randomized?|
|What were the diagnostics or methods used to measure the outcome?||Both|
|Optional: Name of Method or short description||Our outcome of interest was hyperkinetic disorder reported as main diagnosis or as first or second subsidiary diagnosis: (DF90.0, equivalent to ADHD combined type; n = 50), hyperkinetic conduct disorder (DF90.1, equivalent to ADHD with comorbid oppositional defiant disorder or conduct disorder; n = 8) and attention-deficit disorder without hyperactivity (DF98.8, equivalent to ADHD inattentive type; n = 39). Three mutually exclusive groups were defined a priori (Table 1). To fulfil the criteria for ADHD, children must have at least six out of nine symptoms on either the inattention or the hyperactive/impulsive scales. The ADHD group fulfilled DSM-IV criteria for one of the three subtypes: ADHD combined type, ADHD predominantly inattentive type and ADHD predominantly hyperactive/ impulsive type. Subthreshold ADHD was defined as children who lacked one symptom in meeting the criteria for one of the three subtypes. Possible ADHD was defined as children who lacked more than one symptom in meeting the criteria for one of the three. Among children with attention-deficit disorder without hyperactivity (DF98.8), seven had less than five described ADHD symptoms.|
|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.)||Coffee: 0, 1–3, 4–9, >/=10 cups/day Caffeine: <100, 100–399, 400–999, and >/= 1000 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)||adjustments for smoking, alcohol intake, gender of the child, maternal age, family history of psychopathology and parental socio-economic factors; Variables with a biologically plausible effect on the risk of childhood psychopathology and variables reported as risk factors for hyperkinetic disorder and ADHD in other studies were considered potential confounders in the analyses. ATo account for the fact that 6755 women contributed to the study with more than one pregnancy, we used Cox regression with robust standard errors to adjust for possible correlation within the family. We also performed analyses restricted to children of parents without a history of mental illness, children without comorbidities and children born at term (after 37 completed weeks of gestation) and with a birth weight above 2500 g.|
|Provide a general description of results (as reported by the authors).||In the univariate analyses, intrauterine exposure to 10 or more cups per day was associated with a threefold increased risk of hyperkinetic disorder/ADHD. After adjustments for smoking, alcohol intake, gender of the child, maternal age, family history of psychopathology and parental socio-economic factors, the relative risk of exposure to 10 or more cups of coffee per day decreased and became statistically insignificant. Very few women were exposed to high doses of caffeine from sources other than coffee, and when we used all sources of caffeine, we found results similar to those shown for coffee alone. We found that intrauterine exposure to 10 or more cups of coffee per day was associated with a threefold increased risk of hyperkinetic disorder and ADHD. After adjustments for a number of confounding factors, the risk decreased and became statistically insignificant (RR 2.3, 95% CI 0.9–5.9).|
|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?||Prenatal exposure to high levels of coffee was not associated with a statistically significantly increased risk of hyperkinetic disorder and ADHD in the offspring.|
|What were the sources of funding?||The study was financially supported by the Health Insurance Fund (grant nr.2000B521), the Augustinusfonden (grant no.0–1360), Ronald McDonald Charities, Marie Dorthea and Holger From’s Children’s Foundation, Hans and Nora Buchart’s Foundation, Dagmar Marshall’s Foundation.|
|What conflicts of interest were reported?||None reported|
|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.||hyperkinetic disorder + ADHD NOAEL = >/=1,000 mg/day|
|Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot.||The authors present the results of analyses with coffee only; however, they state that the analyses for caffeine from all sources were similar to those with coffee alone. Therefore, the NOAEL selected is stated as caffeine (>/=1,000 mg/day) but the statistical results (RR 2.3, 95% CI 0.9–5.9) are for coffee alone (>/= 10 cups/day). It is assumed that caffeine from all sources would be higher than caffeine from coffee alone, and therefore this should be conservative|
|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.