Study Title and Description
Maternal caffeine intake during pregnancy is associated with birth weight but not with gestational length: results from a large prospective observational 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||Maternal caffeine intake during pregnancy is associated with birth weight but not with gestational length: results from a large prospective observational cohort study.|
|Author||V Sengpiel,E Elind,J Bacelis,S Nilsson,J Grove,R Myhre,M Haugen,HM Meltzer,J Alexander,B Jacobsson,AL Brantsaeter,|
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 examine the association between maternal caffeine intake from different sources and (a) gestational length, particularly the risk for spontaneous preterm delivery (PTD), and (b) birth weight (BW) and the baby being small for gestational age (SGA).|
|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)||This study is based on the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. A total of 59,123 women with uncomplicated pregnancies giving birth to a live singleton were identified. Caffeine intake from different sources was self-reported at gestational weeks 17, 22 and 30. Participants were asked to fill in questionnaires focused on general health status, lifestyle behavior and diet at gestational weeks 15 to 17 (Q1) and 30 (Q3). The MoBa FFQ is a semiquantitative questionnaire designed to record dietary habits and intake of dietary supplements during the first four to five months of pregnancy. At gestational week 22, they completed a food frequency questionnaire (FFQ). Coffee was specified as either filtered, instant, boiled/pressed, decaffeinated, caffè latte/cappuccino, espresso or fig/barley coffee. One cup was defined as 125 ml. In the case of black tea, one cup was defined as 250 ml. One glass of sugar-sweetened or diet cola, energy drink or chocolate milk was defined as 250 ml. Other caffeine sources reported were sandwich spread, desserts, cakes and sweets containing cocoa . Caffeine and nutrient calculations were performed using FoodCalc  and the Norwegian Food Composition Table. Pregnancy and birth records from the Medical Birth Registry of Norway (MBRN) Spontaneous PTD was defined as spontaneous onset of delivery between 22+0 and 36+6 weeks (n = 1,451). The difference between BW and expected BW was calculated as a percentage of expected BW. As there is no consensus, SGA was defined according to ultrasound-based (Marsal, n = 856), population-based (Skjaerven, n = 4,503) and customized (Gardosi, n = 4,733) growth curves. Odds ratios (OR) for caffeine intake and categorical outcome variables were estimated using logistic regression, both unadjusted and adjusted, as above. Statistical significance was assumed for a twosided P value <0.05.|
|How many outcome-specific endpoints are evaluated?||1|
|What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately)||SGA/IUGR|
|List additional health endpoints (separately).|
|List additional health endpoints (separately)|
|Notes||birthweight, gestation length, spontaneous preterm delivery - studied but regression analysis only|
|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||The difference between BW and expected BW was calculated as a percentage of expected BW. BW in grams was registered in the MBRN. As there is still no consensus on standard growth curves, data were analyzed according to three standards based on Northern European populations: ultrasound-based growth curves according to Marsal , population-based growth curves according to Skjaerven  and customized growth curves according to Gardosi . SGA was defined according to the above-mentioned authors’ respective definitions: less than-2 SD (Marsal) or <tenth percentile (Skjaerven, Gardosi). Gestational age in days was determined by second-trimester ultrasound in 98.3% of pregnancies and based on the last menstrual period in the remaining cases. Spontaneous PTD was defined as birth after preterm labor or prelabor rupture of the membranes between 22+0 to 36+6 weeks, while controls delivered spontaneously between 39+0 to 40+6 weeks.|
|Caffeine (general)||Caffeine (general)|
|Energy drinks||Energy drinks|
|Pregnant Women||Pregnant Women|
|What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.)||Caffeine mg/day: 0-50, 51-200, 201-300, >/=300|
|What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models. Copy from methods)||Information on maternal age at delivery and the baby’s sex was available from the MBRN. Parity was based on both MoBa and MBRN data and categorized into number of previous pregnancies of ≥22+0 weeks’ duration. Marital status was defined as either married/cohabiting or not. Self-reported pre-pregnancy height and weight were used to calculate pre-pregnancy body mass index (BMI), which was categorized according to the WHO classification as underweight (<18.5 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight (25 to 29.9 kg/m2) and obese (≥30 kg/m2). Maternal education was categorized as ≤12 years, 13 to 16 years or ≥17 years. History of previous PTD (22+0 to 36+6 weeks of gestation), as registered in the MBRN, was taken into account as a dichotomous variable. Women reported smoking habits during pregnancy in Q1 and were categorized as non-smokers, occasional or daily smokers. Passive smoking and use of other nicotine sources were considered to be dichotomous variables. Alcohol intake from different sources was selfreported in the FFQ (glasses/day, week or month) and calculated in g/day. Persistent nausea at the time of answering the FFQ was used as a dichotomous variable. Household income was categorized as follows: participant and her partner each earning <300,000 Norwegian Krones (NOK)/year, either participant or her partner earning ≥300,000 NOK/year or participant and her partner both earning ≥300,000 NOK/year. In MoBa, more than 99% of the participants are of Caucasian ethnicity; hence ethnicity is not a relevant confounder|
|Provide a general description of results (as reported by the authors).||Total caffeine intake was associated with slightly increased gestational length, that is, 5 h/100 mg/day (95% CI 3 to 8 h, P <10-4 ). However, linear regression with all different caffeine sources included in the same model revealed that only coffee caffeine was significantly associated with gestational length. The diagnosis of SGA varied considerably depending on the growth curve and SGA definition applied. In the adjusted model, intake of an additional 100 mg total caffeine/day was associated with a 21 to 28 g BW decrease, depending on the growth curve. The opposite effect of chocolate caffeine in the Gardosi model was no longer significant after adjustment. Total and coffee caffeine intake was significantly associated with higher odds for SGA, based on logistic regression in all three SGA models, both unadjusted and adjusted. Energy drink and black tea caffeine intake were associated with a significant increase in two of the three SGA models, while there was no significant association with chocolate caffeine. The association of total caffeine intake and BW remained significant when analyses were limited to the non-smoker subgroup (n = 54,136). If the odds for SGA were studied with reference to these recommendations, those 7.7% of women with a daily caffeine intake of 200 to 300 mg had significantly higher odds for SGA (1.27 to 1.62, depending on the SGA definition), in comparison with the lowest (0 to 50 mg/day) caffeine intake group. The odds of giving birth to a SGA infant were 1.62 to 1.66 in the 3.3% of women consuming >300 mg caffeine/day.|
|Did the authors perform a dose-response analysis (or trend/related analysis)?||Yes|
|What were the authors's observations re: trend analysis?||Regression analysis only but visually d-r noted for SGA using either of the definitions|
|What were the author's conclusions?||Coffee intake is associated with slightly increased gestational length but does not affect the odds for spontaneous PTD. It is not caffeine, however, that is the cause of this association. Whether it is some other substance present in coffee, but not in other caffeine sources, or whether coffee drinking is associated, on a behavioral level, with some factor influencing gestational length remains to be further investigated. Caffeine intake is associated with decreased BW and increased odds for SGA. These associations are strengthened by concordant results for different caffeine sources, comparable overall findings regardless of the growth curve or definition of SGA, remaining significance after adjustment, stability over period of pregnancy, consistency with other studies and biological plausibility. These SGA babies might be at higher risk for both short-term and long-term morbidity. As the risk for SGA increases even if pregnant women follow official recommendations in Norway of a maximum caffeine intake of 200 mg/day, this association should be further investigated and recommendations might have to be re-evaluated.|
|What were the sources of funding?||Statement of financial support: the Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and the Norwegian Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS (grant no. 1 UO1 NS 047537-01 and grant no. 2 UOI NS 047537-06A1) and the Norwegian Research Council/ FUGE (grant no. 151918/S10). This study was financially supported by the European Commission, 6th Framework Program, Priority 5 on Food Quality and Safety (FOOD Contract No. 016320 Integrated Project), ‘Newborns and Genotoxic Exposure Risk: Development and application of biomarkers of dietary exposure to genotoxic chemicals and of biomarkers of early effects, using mother-child birth cohorts and biobanks (NewGeneris)’, by the Norwegian Research Council/FUGE (grant no. 183220/S10, FRIMEDKLI-05 ES236011), the Swedish Medical Society (SLS 2008-21198) and Swedish government grants to researchers in public health service (ALFGBG-2863, ALFGBG-11522). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We|
|What conflicts of interest were reported?||The authors declare that they have no competing interests.|
|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.||SGA/IUGR LOAEL = 51-200 mg/day|
|Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot.||ORs for the 3 definitions of SGA at this level were: 1.18 (1.00-1.38; p = 0.04), 1.12 (1.05-1.21; p = 0.001), and 1.09 (1.02-1.17; p = 0.01)|
|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.